The c.776C>T variant in the glucokinase gene, GCK, causes an amino acid change of alanine to valine at codon 259 (p.(Ala259Val)) of NM_000162.5. This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.948, which is greater than the MDEP VCEP threshold of 0.70 (PP3) and is absent from gnomAD v2.1.1 (PM2_Supporting). Additionally, this variant was identified in 15 unrelated individuals with hyperglycemia (PS4; PMID:22035297, internal lab contributors). This variant segregated with diabetes/hyperglycemia, with 16 informative meioses in 5 families (PP1_Strong; PMID: 22035297, 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). Another missense variant, c.775G>A, p.Ala259Thr has been interpreted as pathogenic by the ClinGen MDEP, and p.Ala259Val has a greater Grantham distance (PM5). Lastly, this variant was identified in two individuals with a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and OGTT increment < 3 mmol/L) (PP4_Moderate; internal lab contributors). In summary, c. 776C>T meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PP3, PM2_Supporting, PS4, PP1_Strong, PP2, PM5, PP4_Moderate.