INS and diabetes mellitus: Analysis of rare missense variants classified as likely pathogenic or pathogenic (class 4 or 5) using the ACMG guidelines [45] showed a similar trend, wherein 1.5% of individuals in the early onset diabetes sub-group, 0.4% of individuals in the late onset sub-group, and none of the controls carried such mutations in the GCK, HNF1A, HNF4A, ABCC8, and INS genes (Tables 2 and 3).