Table 2.
Population breakdown and predicted prevalence of afflicted individuals for known pathogenic variants present in the gnomAD database.
| Gene | Consequence | Popn1 | Allele Frequency | Predicted Homozygous (with 95% CIs)2 | USA4 | ||
|---|---|---|---|---|---|---|---|
| Actual | Freq. | Frequency | Global3 | ||||
| PDSS1 | p.Asp308Glu | Ash | 1/9,834 | 1.02E-04 | 1.03E-8 (6.63E-12 – 3.21E-7) | <1 (<1–3) | <1 (<1–1) |
| PDSS2 | p.His92Pro | Afr | 2/23,986 | 8.34E-05 | 6.95E-9 (1.02E-10–9.07E-8) | 8 (<1–107) | <1 (<1–3) |
| Eur | 9/126,452 | 7.12E-05 | 5.07E-9 (1.06E-9–1.83E-8) | 3 (<1–13) | 1 (<1–3) | ||
| p.Gln322* | Eur | 1/111,562 | 8.96E-06 | 8.03E-11 (5.15E-14–2.49E-9) | <1 (<1 – 1) | <1 (<1 –<1) | |
| p.Ser382Leu | EAs | 1/17,240 | 5.80E-05 | 3.36E-9 (2.16E-12 – 1.04E-7) | 5 (<1–168) | <1 (<1 –<1) | |
| Eur | 5/111,682 | 4.48E-05 | 2.0E-9 (2.11E-10–1.09E-8) | 1 (<1–7) | <1 (<1–2) | ||
| Lat | 1/33,582 | 2.98E-05 | 8.87E-10 (5.68E-13–2.75E-8) | <1 (<1–17) | <1 (<1–1) | ||
| COQ2 | p.Ser146Asn | Eur | 4/107,234 | 3.73E-05 | 1.39E-9 (1.03E-10–9.12E-9) | 1 (<1–6) | <1 (<1–1) |
| p.Arg197His | EAs | 1/17,222 | 5.81E-05 | 3.37E-9 (2.16E-12–1.05E-7) | 5 (<1–168) | <1 (<1 –<1) | |
| Eur | 1/111,452 | 8.97E-06 | 8.05E-11 (5.16E-14–2.50E-9) | <1 (<1–1) | <1 (<1 –<1) | ||
| p.Asn228Ser | Eur | 30/126,254 | 2.38E-04 | 5.65E-8 (2.57E-8–1.15E-7) | 41 (18–84) | 11 (5–22) | |
| Afr | 1/23,990 | 4.17E-05 | 1.74E-9 (1.11E-12–5.39E-8) | 2 (<1–63) | <1 (<1–2) | ||
| Lat | 1/34,214 | 2.92E-05 | 8.54E-10 (5.48E-13–2.65E-8) | <1 (<1–16) | <1 (<1–1) | ||
| p.Leu234Argfs*14 | Eur | 1/108,122 | 9.25E-06 | 8.55E-11 (5.48E-14–2.66E-9) | <1 (<1–1) | <1 (<1 –<1) | |
| p.Tyr297Cys | SAs | 1/30,338 | 3.30E-05 | 1.09E-9 (6.96E-13–3.37E-8) | 1 (<1–61) | <1 (<1 –<1) | |
| p.Thr317Met | EAs | 1/11,902 | 8.40E-05 | 7.06E-9 (4.52E-12–2.19E-7) | 11 (<1–353) | <1 (<1–1) | |
| Afr | 1/16,630 | 6.01E-05 | 3.62E-9 (2.32E-12–1.12E-7) | 4 (<1–133) | <1 (<1–4) | ||
| Eur | 3/73,824 | 4.06E-05 | 1.65E-9 (7.02E-11–1.41E-8) | 1 (<1–10) | <1 (<1–2) | ||
| p.Gly390Ala | Lat | 5/33,178 | 1.51E-04 | 2.27E-8 (2.39E-9–1.24E-7) | 14 (1–78) | 1 (<1–6) | |
| Eur | 1/111,216 | 8.99E-06 | 8.08E-11 (5.18E-14–2.51E-9) | <1 (<1–1) | <1 (<1 –<1) | ||
| p.Asn401Ilefs*15 | Eur | 3/110,906 | 2.70E-05 | 7.32E-10 (3.11E-11–6.25E-9) | <1 (<1–4) | <1 (<1–1) | |
| COQ4 | p.Pro64Ser | Eur | 2/97,392 | 2.05E-05 | 4.22E-10 (6.18E-12–5.50E-9) | <1 (<1–4) | <1 (<1–1) |
| p.Asp68His | Lat | 3/28,866 | 1.04E-04 | 1.08E-8 (4.59E-10–9.22E-8) | 6 (<1–58) | <1 (<1–5) | |
| Eur | 6/107,660 | 5.57E-05 | 3.11E-9 (4.18E-10–1.47E-8) | 2 (<1–10) | <1 (<1–2) | ||
| Oth | 1/5,584 | 1.79E-04 | — | — | — | ||
| p.Pro119Leu | Afr | 3/15,302 | 1.96E-04 | 3.84E-8 (1.63E-9–3.28E-7) | 45 (1–389) | 1 (<1–13) | |
| p.Arg145Gly | SAs | 1/26,964 | 3.71E-05 | 1.38E-9 (8.82E-13–4.27E-8) | 2 (<1–77) | <1 (<1 –<1) | |
| p.Arg240Cys | Ash | 31/10,032 | 3.09E-03 | 9.55E-6 (4.41E-6–1.92E-5) | 95 (44–192) | 48 (22–98) | |
| Eur | 9/124,924 | 7.20E-05 | 5.19E-9 (1.09E-9–1.87E-8) | 3 (<1–13) | 1 (<1–3) | ||
| Lat | 2/33,836 | 5.91E-05 | 3.49E-9 (5.12E-11–4.56E-8) | 2 (<1–28) | <1 (<1–2) | ||
| Oth | 5/6,362 | 7.86E-04 | — | — | — | ||
| COQ6 | p.Pro261Leu | Afr | 3/24,026 | 1.25E-04 | 1.56E-8 (6.63E-10–1.33E-7) | 18 (<1–157) | <1 (<1–5) |
| EAs | 2/18,870 | 1.06E-04 | 1.12E-8 (1.65E-10–1.47E-7) | 18 (<1–236) | <1 (<1 –<1) | ||
| Eur | 13/126,674 | 1.03E-04 | 1.05E-8 (2.99E-9–3.08E-8) | 7 (2–22) | 2 (<1–6) | ||
| SAs | 1/30,782 | 3.25E-05 | 1.06E-9 (6.76E-13–3.28E-8) | 1 (<1–59) | <1 (<1 –<1) | ||
| p.Asn380Ser | Afr | 5/24,036 | 2.08E-04 | 4.33E-8 (4.56E-9–2.36E-7) | 51 (5–279) | 1 (<1–9) | |
| EAs | 1/18,870 | 5.30E-05 | 2.81E-9 (1.80E-12–8.72E-8) | 4 (<1–140) | <1 (<1 –<1) | ||
| COQ8A | c.589–3 C > G | Eur | 1/15,000 | 6.67E-05 | 4.44E-9 (2.85E-12–1.38E-7) | 3 (<1–101) | <1 (<1–27) |
| p.Arg213Trp | Eur | 2/14,998 | 1.33E-04 | 1.78E-8 (2.61E-10–2.32E-7) | 13 (<1–169) | 3 (<1–45) | |
| p.Arg213Glnfs*71 | Eur | 1/111,444 | 8.97E-06 | 8.05E-11 (5.16E-14–2.50E-9) | <1 (<1–1) | <1 (<1 –<1) | |
| p.Arg271Cys | Fin | 20/25,144 | 7.95E-04 | 6.33E-7 (2.36E-7–1.51E-6) | 3 (1–8) | <1 (<1 –<1) | |
| Eur | 7/122,222 | 5.73E-05 | 3.28E-9 (5.30E-10–1.39E-8) | 2 (<1–10) | <1 (<1–2) | ||
| Oth | 2/6,304 | 3.17E-04 | — | — | — | ||
| p.Leu277Pro | Eur | 1/99,064 | 1.01E-05 | 1.02E-10 (6.53E-14–3.16E-9) | <1 (<1–2) | <1 (<1 –<1) | |
| p.Arg299Trp | Lat | 3/34,414 | 8.72E-05 | 7.60E-9 (3.23E-10–6.49E-8) | 4 (<1–41) | <1 (<1–3) | |
| Eur | 5/126,472 | 3.95E-05 | 1.56E-9 (1.65E-10–8.51E-9) | 1 (<1–6) | <1 (<1–1) | ||
| p.Ala304Thr | Ash | 1/9,836 | 1.02E-04 | 1.03E-8 (6.63E-12–3.21E-7) | <1 (<1–3) | <1 (<1–1) | |
| Afr | 1/15,270 | 6.55E-05 | 4.29E-9 (2.75E-12–1.33E-7) | 5 (<1–157) | <1 (<1–5) | ||
| SAs | 1/30,782 | 3.25E-05 | 1.06E-9 (6.76E-13–3.28E-8) | 1 (<1–59) | <1 (<1 –<1) | ||
| Eur | 1/111,486 | 8.97E-06 | 8.05E-11 (5.16E-14–2.50E-9) | <1 (<1–1) | <1 (<1 –<1) | ||
| p.Ala304Val | Eur | 10/126,438 | 7.91E-05 | 6.26E-9 (1.44E-9–2.12E-8) | 4 (1–15) | 1 (<1–4) | |
| Oth | 1/6,456 | 1.55E-04 | — | — | — | ||
| p.Arg348* | Lat | 3/31,814 | 9.43E-05 | 8.89E-9 (3.78E-10–7.59E-8) | 5 (<1–48) | <1 (<1–4) | |
| Eur | 7/110,946 | 6.31E-05 | 3.98E-9 (6.44E-10–1.69E-8) | 2 (<1–12) | <1 (<1–3) | ||
| p.Leu379* | Eur | 1/111,658 | 8.96E-06 | 8.02E-11 (5.14E-14–2.49E-9) | <1 (<1–1) | <1 (<1 –<1) | |
| p.Arg410* | EAs | 2/18,820 | 1.06E-04 | 1.13E-8 (1.66E-10–1.47E-7) | 18 (<1–237) | <1 (<1 –<1) | |
| SAs | 1/30,750 | 3.25E-05 | 1.06E-9 (6.78E-13–3.28E-8) | 1 (<1–59) | <1 (<1 –<1) | ||
| Eur | 2/125,096 | 1.60E-05 | 2.56E-10 (3.75E-12–3.34E-9) | <1 (<1–2) | <1 (<1 –<1) | ||
| p.Thr445Argfs*52 | Lat | 1/33,562 | 2.98E-05 | 8.88E-10 (5.69E-13–2.76E-8) | <1 (<1–17) | <1 (<1–1) | |
| p.Thr511Met | Lat | 5/34,420 | 1.45E-04 | 2.11E-8 (2.22E-9–1.15E-7) | 13 (1–72) | 1 (<1–6) | |
| Ash | 1/10,150 | 9.85E-05 | 9.71E-9 (6.22E-12–3.01E-7) | <1 (<1–3) | <1 (<1–1) | ||
| Eur | 7/126,688 | 5.53E-05 | 3.05E-9 (4.94E-10–1.30E-8) | 2 (<1–9) | <1 (<1–2) | ||
| p.Gly549Ser | Eur | 30/126,484 | 2.37E-04 | 5.63E-8 (2.56E-8–1.15E-7) | 41 (18–83) | 11 (5–22) | |
| Fin | 2/25,596 | 7.81E-05 | 6.11E-9 (8.95E-11–7.97E-8) | <1 (<1 –<1) | <1 (<1 –<1) | ||
| Afr | 1/23,988 | 4.17E-05 | 1.74E-9 (1.11E-12–5.39E-8) | 2 (<1–63) | <1 (<1–2) | ||
| Lat | 1/34,410 | 2.91E-05 | 8.45E-10 (5.41E-13–2.62E-8) | <1 (<1–16) | <1 (<1–1) | ||
| Oth | 1/6,456 | 1.55E-04 | — | — | — | ||
| p.Glu551Lys | Eur | 4/126,382 | 3.17E-05 | 1.0E-9 (7.44E-11–6.57E-9) | <1 (<1–4) | <1 (<1–1) | |
| Oth | 1/6,454 | 1.55E-04 | — | — | — | ||
| p.Met555Ile | Fin | 18/24,584 | 7.32E-04 | 5.36E-7 (1.88E-7–1.34E-6) | 2 (1–7) | <1 (<1 –<1) | |
| Eur | 21/126,250 | 1.66E-04 | 2.77E-8 (1.06E-8–6.46E-8) | 20 (7–47) | 5 (2–12) | ||
| Oth | 2/6,446 | 3.10E-04 | — | — | — | ||
| p.Glu568* | Eur | 1/111,654 | 8.96E-06 | 8.02E-11 (5.14E-14–2.49E-9) | <1 (<1–1) | <1 (<1 –<1) | |
| p.Ser582Glufs*148 | Lat | 1/33,580 | 2.98E-05 | 8.87E-10 (5.68E-13–2.75E-8) | <1 (<1–17) | <1 (<1–1) | |
| Eur | 3/111,712 | 2.69E-05 | 7.21E-10 (3.07E-11–6.16E-9) | <1 (<1–4) | <1 (<1–1) | ||
| p.Thr584del | Ash | 26/9,848 | 2.64E-03 | 6.97E-6 (2.98E-6–1.49E-5) | 69 (29–149) | 35 (15–76) | |
| Eur | 4/111,702 | 3.58E-05 | 1.28E-9 (9.52E-11–8.41E-9) | <1 (<1–6) | <1 (<1–1) | ||
| p.Pro602Arg | Ash | 3/10,148 | 2.96E-04 | 8.74E-8 (3.72E-9–7.46E-7) | <1 (<1–7) | <1 (<1–3) | |
| Lat | 2/34,420 | 5.81E-05 | 3.38E-9 (4.95E-11–4.41E-8) | 2 (<1–27) | <1 (<1–2) | ||
| SAs | 1/30,782 | 3.25E-05 | 1.06E-9 (6.76E-13–3.28E-8) | 1 (<1–59) | <1 (<1 –<1) | ||
| Eur | 2/126,676 | 1.58E-05 | 2.49E-10 (3.66E-12–3.25E-9) | <1 (<1–2) | <1 (<1 –<1) | ||
| Oth | 1/6,464 | 1.55E-04 | — | — | — | ||
| p.Pro602Gln | SAs | 2/30,782 | 6.50E-05 | 4.22E-9 (6.19E-11–5.51E-8) | 7 (<1–100) | <1 (<1 –<1) | |
| Eur | 7/111,706 | 6.27E-05 | 3.93E-9 (6.35E-10–1.67E-8) | 2 (<1–12) | <1 (<1–3) | ||
| Oth | 1/5,486 | 1.82E-04 | — | — | — | ||
| p.Ser616Leufs*114 | EAs | 6/18,866 | 3.18E-04 | 1.01E-7 (1.36E-8–4.79E-7) | 163 (21–772) | <1 (<1–2) | |
| SAs | 4/30,782 | 1.30E-04 | 1.69E-8 (1.25E-9–1.11E-7) | 30 (2–201) | <1 (<1 –<1) | ||
| Afr | 1/24,020 | 4.16E-05 | 1.73E-9 (1.11E-12–5.38E-8) | 2 (<1–63) | <1 (<1–2) | ||
| Eur | 5/126,684 | 3.95E-05 | 1.56E-9 (1.64E-10–8.48E-9) | 1 (<1–6) | <1 (<1–1) | ||
| COQ8B | p.Phe215Leufs*14 | Eur | 1/107,204 | 9.33E-06 | 8.70E-11 (5.58E-14–2.70E-9) | <1 (<1–1) | <1 (<1 –<1) |
| p.Phe215Leufs*14 | Eur | 7/122,270 | 5.73E-05 | 3.28E-9 (5.30E-10–1.39E-8) | 2 (<1–10) | <1 (<1–2) | |
| EAs | 1/18,840 | 5.31E-05 | 2.82E-9 (1.81E-12–8.74E-8) | 4 (<1–140) | <1 (<1 –<1) | ||
| Lat | 1/34,350 | 2.91E-05 | 8.48E-10 (5.43E-13–2.63E-8) | <1 (<1–16) | <1 (<1–1) | ||
| Oth | 1/6,400 | 1.56E-04 | — | — | — | ||
| p.Asp286Gly | Fin | 4/24,036 | 1.66E-04 | 2.77E-8 (2.06E-9–1.82E-7) | <1 (<1 –<1) | <1 (<1 –<1) | |
| p.Arg320Trp | Afr | 2/15,262 | 1.31E-04 | 1.72E-8 (2.52E-10–2.24E-7) | 20 (<1–265) | <1 (<1–9) | |
| SAs | 2/30,780 | 6.50E-05 | 4.22E-9 (6.19E-11–5.51E-8) | 7 (<1–100) | <1 (<1 –<1) | ||
| Eur | 1/111,380 | 8.98E-06 | 8.06E-11 (5.17E-14–2.50E-9) | <1 (<1–1) | <1 (<1 –<1) | ||
| p.His400Glnfs*11 | Eur | 1/111,710 | 8.95E-06 | 8.01E-11 (5.14E-14–2.49E-9) | <1 (<1–1) | <1 (<1 –<1) | |
| p.Glu447Glyfs*10 | Eur | 6/108,260 | 5.54E-05 | 3.07E-9 (4.14E-10–1.46E-8) | 2 (<1–10) | <1 (<1–2) | |
| p.Glu483* | SAs | 10/29,404 | 3.40E-04 | 1.16E-7 (2.66E-8–3.91E-7) | 210 (48–712) | <1 (<1–1) | |
| Eur | 1/101,248 | 9.88E-06 | 9.75E-11 (6.25E-14–3.03E-9) | <1 (<1–2) | <1 (<1 –<1) | ||
| COQ9 | c.521 + 1delG | Eur | 1/111,218 | 8.99E-06 | 8.08E-11 (5.18E-14–2.51E-9) | <1 (<1–1) | <1 (<1 –<1) |
| p.Arg244* | Fin | 2/22,296 | 8.97E-05 | 8.05E-9 (1.18E-10–1.05E-7) | <1 (<1 –<1) | <1 (<1 –<1) | |
| SAs | 1/30,782 | 3.25E-05 | 1.06E-9 (6.76E-13–3.28E-8) | 1 (<1–59) | <1 (<1 –<1) | ||
| Totals: | 1,016 (200–6956) | 122 (49–444) | |||||
1 Ashkenazi Jewish, African/African American, European (non-Finnish), East Asian, South Asian, Latin American (admixed American), Finnish, Other.
2Predicted homozygosity assuming Hardy-Weinberg equilibrium.
3Predicted number of homozygotes in population size equivalent to that of the given ethnicity globally.
4Predicted number of homozygotes in a population size equivalent to that the given ethnicity in the USA.