The c.1255T>G variant in the glucokinase gene, GCK, causes an amino acid change of alanine to proline at codon 419 (p.(Phe419Val)) of NM_000162.5. GCK is defined by the ClinGen MDEP VCEP as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.991, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Another missense variant, c.1256T>C (p.Phe419Ser), has been classified as likely pathogenic by the ClinGen MDEP VCEP (PM5_Supporting). This variant segregated with the disease with two informative meioses in a single family with diabetes, however, this does not meet the thresholds for PP1 set by the ClinGen MDEP VCEP (PMID: 27236918, internal lab contributors). This variant was identified in an individual with diabetes, however, PP4 is unable to be evaluated due to incomplete clinical information. In summary, this variant meets the criteria to be classified as uncertain significance for GCK-MODY. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.2.0, approved 6/7/2023): PP2, PP3, PM2_Supporting, PM5_Supporting.