The c.142G>A variant in the glucokinase gene, GCK, causes an amino acid change of glutamic acid to lysine at codon 48 (p.(Glu48Lys)) 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). The Popmax filtering allele frequency of the c.142G>A variant in gnomAD v2.1.1 is 0.00001685, which falls between ClinGen MDEP-established cutoffs for PM2_Supporting (0.000003) and BS1 (0.00004); thus, neither criterion will be applied. 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 variant was observed in unknown phase in that individual with the variant c.461T>G p.Val154Gly (internal lab contributors), which is classified as likely pathogenic by the ClinGen MDEP (BP2). This variant segregated with hyperglycemia with two informative meioses in a single family; however, this does not meet the thresholds for PP1 set by the ClinGen MDEP (PMID: 27236918, internal lab contributors). This variant was identified in an individual with normal fasting glucose (BS2; PMID: 23799006, internal lab contributor). This variant has a REVEL score of 0.6959, which is between the ClinGen MDEP thresholds for BP4 and PP3, predicting neither a damaging nor benign impact on GCK function. In summary, c.142G>A meets the criteria to be classified as likely benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): BS2, PP4_Moderate, BP2, PP2.