The c.1190G>A variant in the glucokinase gene, GCK, causes an amino acid change of Arg to His at codon 397 (p.(Arg397His)) of NM_000162.5. Another missense variant, c.1190G>T p.Arg397Leu, has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.Arg397His (PM5_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 is absent from gnomAD v2.1.1 (PM2_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.779 which is greater than the MDEP VCEP threshold of 0.70 (PP3). 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 was identified in 5 unrelated individuals with non- autoimmune and non-absolute/near-absolute insulin-deficient diabetes (PS4_Moderate; internal lab contributors). This variant segregated with diabetes/hyperglycemia, with 2 informative meioses in 2 families with MODY (PP1; internal lab contributors). In summary, c.1190G>A 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): PM5_Supporting, PP2, PM2_Supporting, PP3, PP4, PS4_Moderate, PP1.