The c.737T>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of valine to glycine at codon 246 (p.(Val2466Gly)) 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). It is also predicted to be deleterious by computational evidence, with a REVEL score of 0.947, which is greater than the MDEP VCEP threshold of 0.70 (PP3). Another missense variant, c.736G>T (p.Val246Leu)​ has been interpreted as pathogenic by the ClinGen MDEP and has a greater Grantham distance (PM5). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors). One of these individuals has a MODY probability calculator result below 50% but has had persistent C-peptide for 27 years, and had negative genetic testing for HNF4A) (PP4; internal lab contributor). Taken together, this evidence supports the classification of this variant as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 6/4/2021): PM5, PP3, PP4, PM1_Supporting, PM2_Supporting.