The c.170T>A variant in the glucokinase gene, GCK, causes an amino acid change of methionine to lysine at codon 57 (p.(Met57Lys)) of NM_000162.5. This variant is absent from gnomAD v4.1.0 (PM2_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 predicted to be deleterious by computational evidence, with a REVEL score of 0.98, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant was identified in three unrelated individuals with hyperglycemia; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (PMID: 39859454, ClinVar ID: 2684202, internal lab contributors). At least one of these individuals had a clinical history highly specific for GCK-hyperglycemia (multiple instances of fasting glucose 5.5-8 mmol/L and HbA1c 5.6 - 7.6%, and negative antibodies) (PP4_Moderate; internal lab contributors). This variant segregated with hyperglycemia with at least 3 meioses in a single family (PP1; internal lab contributors). Another missense variant at the same codon, c.171G>A, p.(Met57Ile), has been interpreted as pathogenic by the ClinGen MDEP, and p.(Met57Lys) has a greater Grantham distance (PM5). In summary, c.170T>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 2.0.0, approved 2/17/2025): PM2_Supporting, PP1, PP2, PP3, PP4_Moderate, PM5.