The c. variant in the glucokinase gene, GCK, causes an amino acid change of leucine to arginine at codon 386 (p.(Leu386Arg)) 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 was identified in 3 unrelated individuals with hyperglycemia; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors). Two other missense variants, c.1156C>G p.Leu386Val and c.1157T>C p.Leu386Pro, have been interpreted as pathogenic by the ClinGen MDEP, and p.Leu386Arg has a greater Grantham distance than p.Leu386Val and p.Leu386Pro (PM5_Strong). In summary, c.1157T>G 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): PM5_Strong, PP2, PP3, PM2_Supporting.