Table 1.

ClinVar pathogenic mutations predicted to be rescued by BPN-15477 treatment and selected based on top populational allele frequencies in gnomAD (v2.1.1).

Gene	Mutation	Frequency	Molecular consequence (ClinVar)	Splicing (SpliceAI)	Predicted drug response	Disease
IL36RN	c.115 + 6T > C	1.00E−03	Intronic	Loss	Inclusion	Pustular psoriasis
LIPA	c.894G > A	8.28E−04	Synonymous	Loss	Inclusion	Lysosomal acid lipase deficiency
DNAH9	c.1970 + 4A > G	3.18E−04	Intronic	Loss	Inclusion	Ciliary dyskinesia
CA5A	c.555G > A	1.67E−04	Synonymous	Loss	Inclusion	Carbonic anhydrase VA deficiency
ORC6	c.449 + 5G > A	1.63E−04	Intronic	Loss	Inclusion	Meier-Gorlin syndrome 3
SRD5A2	c.547G > A	1.59E−04	Missense	Loss	Inclusion	3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency
DGUOK	c.591G > A	1.27E−04	Intronic/synonymous	Loss	Inclusion	Mitochondrial DNA-depletion syndrome 3
HBB	c.92G > A	1.03E−04	Missense	Loss	Inclusion	Beta thalassemia
PIGN	c.963G > A	8.31E−05	Synonymous	Loss	Inclusion	Multiple congenital anomalies-hypotonia-seizures syndrome 1
NPHP1	c.1027G > A	6.37E−05	Missense	Loss	Inclusion	Nephronophthisis
KDSR	c.879G > A	6.37E−05	Synonymous	Loss	Inclusion	Erythrokeratodermia variabilis et progressive 4
SLC12A1	c.1942G > A	6.37E−05	Missense	Loss	Inclusion	Bartter syndrome, type 1
NSD1	c.6152-5T > G	5.96E−05	Intronic	Loss	Inclusion	Beckwith-Wiedemann syndrome
PARN	c.659 + 4_659 + 7delAGTA	4.63E−05	Intronic	Loss	Inclusion	Dyskeratosis congenita
GLA	c.639 + 919 G > A	4.53E−05	Intronic	Gain	Exclusion	Fabry disease
ATM	c.2250G > A	4.39E−05	Synonymous	Loss	Inclusion	Ataxia-telangiectasia syndrome
POLG	c.3104 + 3A > T	3.98E−05	Intronic	Loss	Inclusion	Progressive sclerosing poliodystrophy
GPX4	c.476 + 5G > A	3.65E−05	Intronic	Loss	Inclusion	Spondylometaphyseal dysplasia
GYPA	c.232G > A	3.60E−05	Missense	Loss	Inclusion	Blood group erik
MYO7A	c.2904G > A	3.20E−05	Synonymous	Loss	Inclusion	Usher syndrome, type 1