While the ExAC dataset exceeds the scale of previously available frequency reference datasets, much remains to be gained by further increases in sample size. Indeed, the fact that even the rarest transversions have mutational rates11 on the order of 1 × 10−9 implies that the vast majority of possible non-lethal SNVs likely exist in some living human. ExAC already includes >63% of all possible protein-coding CpG transitions at well-covered synonymous sites; orders-of-magnitude increases in sample size will eventually lead to saturation of other classes of variation.
