The association of LoF alleles in MC4R with type 2 diabetes was validated using exome sequencing data from the T2D Knowledge Portal; odds ratio (OR) for carriers of rare LoF variants versus noncarriers, 1.59; 95% confidence interval (CI), 1.22–2.08; p = 0.0007; Pheterogeneity compared to the estimate in UK Biobank from this study = 0.21. This evidence concerns the gene MC4R and type 2 diabetes mellitus.