The c.388C>T variant in the HNF1 homeobox A gene, HNF1A, results in a premature termination at codon 130 (p.(Gln130Ter)) of NM_000545.8. This variant, located in biologically-relevant exon 2 of 10, is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID: 23348805). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in seven unrelated (though part of a population isolate and likely having a common ancestor) individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4_Moderate; internal lab contributors). This variant was segregated with diabetes, with eight informative meioses in four families with MODY (PP1_Strong; internal lab contributors). This variant was identified in at least 3 individuals with a clinical history highly specific for HNF1A-monogenic diabetes (MODY probability calculator result >75%, negative genetic testing for HNF4A, and negative antibodies) (PP4_Moderate; internal lab contributors). In summary, c.388C>T meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.1.0, approved 8/11/2023): PVS1, PM2_supporting, PS4_moderate, PP1_strong, PP4_Moderate.