Rare variants of a disease are generally assumed to have a significant effect on the phenotype, however, potential ascertainment biases in Mendelian genetic studies occur, even for rare variants of HNF1A that have been shown to cause MODY3 owing to the selection of patients with overt diabetes or a family history of MODY [76,93,95]. The gene discussed is HNF1A; the disease is MODY.