Among the 7,404,909 HQ variants in ExAC, we found 179,774 high-confidence PTVs (as defined in Supplementary Information Section 6), 121,309 of which are singletons. This corresponds to an average of 85 heterozygous and 35 homozygous PTVs per individual (Figure 5a). The diverse nature of the cohort enables the discovery of substantial numbers of novel PTVs: out of 58,435 PTVs with an allele count greater than one, 33,625 occur in only one population. However, while PTVs as a category are extremely rare, the majority of the PTVs found in any one person are common, and each individual has only ~2 singleton PTVs, of which 0.14 are found in PTV-constrained genes (pLI >0.9). ExAC recapitulates known aspects of population demographic models, including an increase in intermediate-frequency (1–5%) PTVs in Finland32 and relatively common (>1%) PTVs in Africans (Figure 5b). However, these differences are diminished when considering only LoF-constrained (pLI > 0.9) genes (Extended Data Figure 4).
