a, The Discovery case cohort shows a 2.5-fold enrichment for ultra-rare (0.001% > MAF > 0%) alleles compared to controls. b, The Replication cohort shows a 2-fold enrichment of such alleles compared to the exome control cohort. c, The BBS case meta-analysis shows a 2.2-fold enrichment compared to the combined control cohorts. d, Collapsed cohorts. a–d show plots across four MAF bins (1% > MAF > 0.5%, 0.5% > MAF > 0.1%, 0.1% > MAF > 0.001%, and 0.001% > MAF > 0%).