The c.824G>T variant in the glucokinase gene, GCK, causes an amino acid change of arginine to leucine at codon 275 (p.(Arg275Leu)) of NM_000162.5. This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and negative antibodies) (PP4_Moderate; internal lab contributors). 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 predicted to be deleterious by computational evidence, with a REVEL score of 0.702, 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.823C>T p.Arg275Cys, has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.Arg275Leu (PM5_Supporting). In summary, c.824G>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): PP4_Moderate, PP2, PP3, PM2_Supporting, PM5_Supporting.