The c.532G>A variant in the glucokinase gene, GCK, causes an amino acid change of glycine to arginine at codon 178 (p.(Gly178Arg)) 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 0.979, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant has an incomputable gnomAD v4.1 Grpmax filtering allele frequency due to 1 copy in the European non-Finnish subpopulation and no copies in any other subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (Grpmax FAF <= 0.000003) (PM2_Supporting). This variant was identified in five unrelated individuals with hyperglycemia (PS4_Moderate; PMID: 36257325,11508276; internal lab contributors). At least one of these individuals had a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and OGTT with minimal increment (<3mmol/l) (PP4_Moderate; internal lab contributors). Another missense variant at the same residue, c.533G>A p.Gly178Glu, has been interpreted as pathogenic by the ClinGen MDEP, and p.Gly178Arg has a greater Grantham distance (PM5). In summary, c.532G>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 3.1.0, approved 10/10/2025): PP2, PP3, PM2_Supporting, PM5, PP4_Moderate, PS4_Moderate.