The NM_000156.6:c.115A>G variant in GAMT is predicted to results in the missense substitution of lysine by glutamate at amino acid 39 (p.Lys39Glu). One proband with this variant has been reported with moderate global developmental delay, increased guanidinoacetate and significantly reduced creatine in dried blood spots, and significantly decreased creatine peak on MRS (PMID:37305710) (PP4_Strong). This individual is compound heterozygous for the variant and another variant in GAMT that has been classified as pathogenic for GAMT deficiency by the ClinGen CCDS VCEP, c.328-2A>G (ClinVar Variation ID: 854099); the phase is unknown (PMID:3730571) (0.5 points) (PM3_Supporting). The variant is absent from gnomAD v4.1.0 (PM2_Supporting). The computational predictor REVEL gives a score of 0.721, evidence that correlates with impact to GAMT function at the supporting level (PMID: 36413997) (PP3). In summary, this variant meets the criteria to be classified as Likely Pathogenic for GAMT deficiency based on the GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 2.0.0). PM2_Supporting, PP4_Strong, PP3, PM3_Supporting. (Classification approved by the ClinGen CCDS VCEP on April 20, 2026).