The c.1189C>G variant in the glucokinase gene, GCK, causes an amino acid change of arginine to glycine at codon 397 (p.(Arg397Glyr)) 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 0.817, which is greater than or equal to the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in two related individuals with a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6%) (PP4; internal lab contributors). This variant segregated with diabetes with two informative meioses in a single family, however this does not meet the thresholds for PP1 set by the ClinGen MDEP VCEP (PMID: 27236918, internal lab contributor). Another missense variant, c.1190G>T p.Arg397Leu, has been interpreted as pathogenic by the ClinGen MDEP VCEP and p.Arg397Gly has a greater Grantham distance(PM5). In summary, c.1189C>G 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 1.3.0, approved 8/11/2023): PM5, PP2, PP3, PP4, PM2_Supporting.