The c.827C>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of alanine to glycine at codon 276 (p.(Ala276Gly)) of NM_000545.8. This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant also is predicted to be deleterious by computational evidence, with a REVEL score of 0.901, which is greater than the MDEP VCEP threshold of 0.70 (PP3). Additionally, this variant has a minor allele frequency of 0.000007816 in the gnomAD v2.1.1 European non-Finnish population and one copy in another subpopulation, which is less than the ClinGen MDEP threshold for PM2_Supporting (≤0.00002 and ≤1 copy in any other subpopulation) (PM2_Supporting). This variant was identified in 6 unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4_Moderate; internal lab contributors). At least one of these individuals had a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, antibody negative, and response to low dose sulfonylureas) (PP4_Moderate; internal lab contributor). Another missense variant, c.827C>A (p.Ala276Asp), has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.Ala276Gly (PM5_Supporting). In summary, c.827C>G meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM1_Supporting, PP3, PM2_Supporting, PS4_Moderate, PP4_Moderate, PM5_Supporting.