The c.952G>T variant in the glucokinase gene, GCK, causes an amino acid change of glycine to tryptophan at codon 318 (p.(Gly318Trp)) 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 has an incomputable gnomAD v4.1.0 Grpmax filtering allele frequency due to zero copies in the European non-Finnish subpopulation and 1 copy in any other subpopulation, thereby meeting the ClinGen MDEP threshold criteria for PM2_Supporting (ENF Grpmax FAF <= 0.000003) (PM2_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.9, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant was identified in a single individual with hyperglycemia; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold and PP4 cannot be evaluated due to insufficient clinical data (internal lab contributors). Another missense variant, c.952G>A, p.(Gly318Arg) has been interpreted as pathogenic by the ClinGen MDEP, and p.(Gly318Trp) has a greater Grantham distance (PM5). In summary, c.952G>T meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/23): PM5, PM2_Supporting, PP2, PP3.