The c.106G>T variant in the glucokinase gene,GCK, causes an amino acid change of arginine to tryptophan at codon 36 (p.(Arg36Trp)) of NM_000162.5. While the Popmax filtering allele frequency is 0.000002920 (European non-Finnish population), which is less than the MDEP cutoff for PM2_Supporting, there are two copies of the variant in the African/African American subpopulation; therefore, PM2_Supporting cannot be applied, and PS4 cannot be applied regardless of the number of cases. 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 0.911, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant was identified in an individual with a clinical history highly specific for GCK-MODY (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6%) (PP4; PMID: 16965331). This variant was identified as a de novo occurrence with confirmed parental relationships in an individual with diabetes, but whose clinical picture is not highly specific for GCK-MODY (PS2_Moderate; PMID:8168652). This variant segregated with diabetes, with five informative meioses in three families with MODY (PP1_Strong; PMIDs: 17573900, 23433541, 33477506). In summary, c.106C>T meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PP2, PP3, PP4, PS2_Moderate, PP1_Strong,