The ExAC resource provides the largest database to date for the estimation of allele frequency for protein-coding genetic variants, providing a powerful filter for analysis of candidate pathogenic variants in severe Mendelian diseases. Frequency data from ESP1 have been widely used for this purpose, but those data are limited by population diversity and by resolution at allele frequencies ≤0.1%. ExAC therefore provides substantially improved power for Mendelian analyses, although it is still limited in power at lower allele frequencies, emphasizing the need for more sophisticated pathogenic variant filtering strategies alongside on-going data aggregation efforts.
