FIND: a software tool for identifying population-enriched pathogenic variants in gnomAD

Founder mutations are variants that arose in a single ancestor and became enriched in a descendant population through a bottleneck and endogamy. Identification of pathogenic founder mutations has facilitated efficient targeted screening. More broadly, even without confirmed founder status, identifying pathogenic variants that are enriched within specific populations reveals population-specific disease burden. However, many such variants remain hidden in plain sight within existing datasets. To address this gap, we developed FIND (Founder candidates hidden IN Data), a web tool that identifies pathogenic, likely pathogenic, and predicted loss-of-function variants in gnomAD with frequencies >0.00008 in one ancestry group and at least tenfold higher than in all others (after zeroing populations with four or fewer observed alleles). Testing FIND on the genes FLNC, TMEM127, MYH7, and BRCA2 confirmed its utility and functionality by identifying nine well-known founder mutations and seven candidate founders. Candidates enriched in African American and admixed American populations were validated with the All of Us database, highlighting the utility of this approach for populations historically underrepresented in genetic studies. Source code is freely available at https://github.com/aacoder105/FIND under an MIT license, with a web interface at https://ethnic-variant-mutation-finder.onrender.com/.