The c.1175G>T variant in the glucokinase gene, GCK, causes an amino acid change of Arg to Leu at codon 392 (p.(Arg392Leu)) of NM_000162.5. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant has a REVEL score of 0.568, which is between the ClinGen MDEP thresholds, predicting neither a damaging nor benign impact on GCK function. Another missense variant, c.1174C>T p.Arg392Cys, has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.Arg392Leu (PM5_Supporting). This variant was identified in 4 unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4_Moderate; internal lab contributors). This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6%)(PP4; internal lab contributors). This variant segregated with diabetes, with 3 informative meioses in 2 families with MODY (PP1_Moderate; internal lab contributors). In summary, c.1175G>T meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PM2_Supporting, PP2, PM5_Supporting, PS4_Moderate, PP4, PP1_Moderate.