The c.1373_1376del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 458 (NM_000162.5), adding 155 novel amino acids before encountering a stop codon (p.(Lys458ArgfsTer155)). This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256), This variant is absent from gnomAD v2.1.1 (PM2_Supporting). 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; internal lab contributors). This variant segregated with disease with 3 informative meioses in 1 family with MODY (PP1; internal lab contributors). In summary, the c.1373_1376del variant meets the criteria to be classified as pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PVS1, PM2_Supporting, PP4, PP1.