Genome-wide association and next-generation sequencing studies of randomly ascertained individuals have challenged binary assumptions and overinflated pathogenicity estimates regarding variants in HNF1A (and other Mendelian disease genes) and identified common coding variants of low effect associated with increased risk of type 2 diabetes (MIM: 125853).5, 6, 7, 8 Whole-exome sequencing studies in populations of Mexican American ancestry have revealed a low-frequency missense variant (c.1522G>Α [p.Glu508Lys]) in HNF1A associated with a 5-fold increase in type 2 diabetes prevalence.3 This evidence concerns the gene HNF1A and type 2 diabetes mellitus.