The c.567C>G variant in the glucokinase gene, GCK, causes an amino acid change of isoleucine to methionine, at codon 189 (p.(Ile189Met)) of NM_000162.5. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Additionally, 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). Another missense variant, c.566T>C, p.Ile189Thr, has been classified as pathogenic by the ClinGen MDEP but has a greater Grantham distance than p.Ile189Met (PM5_Supporting). Additionally, this variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.841, which is greater than the MDEP threshold of 0.70 (PP3). This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and negative antibodies)(PP4_Moderate, internal lab contributors). This occurred in this individual as a de novo occurrence with unconfirmed parental relationships (PS2_Moderate; internal lab contributor). While this variant was identified in the individual mentioned above, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributor). In summary, this variant meets the criteria to be classified as likely pathogenic for monogenic diabetes. AMCG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.3.0, approved 8/11/2023): PP4_Moderate, PM2_Supporting, PM5_Supporting, PP2, PP3, PS2_Moderate.