The c.1088A>G variant in the glucokinase gene, GCK, causes an amino acid change of aspartic acid to glycine at codon 363 (p.(Asp363Gly)) of NM_000162.5. This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.937, which is greater than the MDEP VCEP threshold of 0.70 (PP3). 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 is absent from gnomAD v4.1.0(PM2_Supporting). This variant was identified in an individual with a clinical history highly specific for GCK-MODY (fasting glucose 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and three-generation, dominant family history of diabetes (in a family not used for PP1)) (PP4_Moderate; internal lab contributors). This variant segregated with hyperglycemia, with 4 informative meioses in 2 families (PP1_Strong; internal lab contributors). This variant was identified in four unrelated individuals with hyperglycemia (PS4_Moderate; PMID: 37045781, internal lab contributors). In summary, c.1088A>G meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 3.0.0, approved 7/23/2025): PS4_Moderate, PP4_Moderate, PP1_Strong, PM2_Supporting, PP2, PP3.