The c.1175G>C variant in the glucokinase gene, GCK, causes an amino acid change of alanine to proline at codon 392 (p.(Arg392Pro)) of NM_000162.5. GCK is defined by the ClinGen MDEP VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.909, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Another missense variant, c.1174C>T p.Arg392Cys, has been classified as pathogenic by the ClinGen MDEP VCEP but has a greater Grantham distance than p.Arg392Pro (PM5_Supporting). This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L, HbA1c 5.6 - 7.6%, OGTT increment < 3 mmol/L, and 3 generation family history of diabetes/hyperglycemia)(PP4_Moderate; internal lab contributors). This variant was identified in two unrelated individuals with a clinical picture consistent with monogenic diabetes; however, PS4_Moderate cannot be applied because this number is below the MDEP threshold (PMID 23624530, internal lab contributors). In summary, this variant meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.2.0, approved 6/7/2023).: PP2, PP3, PM2_Supporting, PP4_Moderate, PM5_Supporting.