We next examined the distribution of LoFs and missense and synonymous variants by gene and observed disparity among genes as some are depleted of LoF (such as SIX1 [MIM: 601205]) whereas others are enriched in synonymous (such as ACTG1) or missense (such as ADGRV1) variants (Figures 5B and S4A). Of all LoF variants, the fraction contributing to the P/LP pool differs across genes, showing that for some genes a LoF variant is most likely to be pathogenic (SOX10 [MIM: 602229], TCOF1 [MIM: 606847], COL2A1 [MIM: 120140], COL4A5 [MIM: 303630], EYA1 [MIM: 601653], GATA3 [MIM: 131320], POU3F4 [MIM: 300039]), whereas for others it is not (e.g., ACTG1, AIFM1 [MIM: 300169]) (Figures 5C and S4B). A similar disparity is also observed for missense variants, where for some genes more than half of all missense variants are P/LP (GJB2, KCNQ1, PRPS1 [MIM: 311850]) and for others this contribution is marginal (e.g., TRIOBP [MIM: 609761], ADGRV1) (Figures 5D and S4C). Interestingly, for some genes such as BSND (MIM: 606412), TCOF1, and TRIOBP, approximately half of all missense variants are classified as B/LB, implying that a missense variant in those genes is more likely to be non-disease causing.