The c.167A>C variant in the glucokinase gene, GCK, causes an amino acid change of lysine to threonine at codon 56 (p.(Lys56Thr)) of NM_000162.5. 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 0.957, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). 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). This variant segregated with diabetes, with 3 informative meioses in 2 families (PP1_Moderate; internal lab contributors). This variant was identified in 4 unrelated individuals with hyperglycemia (PS4_Moderate; PMID: 33852230, ClinVar VCV001807279.3, Internal lab contributors). In summary, c.167A>C 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, approved 8/11/2023): PP4_Moderate, PP2, PP3, PP1_Moderate, PM2_Supporting, PS4_Moderate.