The NM_000156.6:c.59G>T variant in GAMT is a missense variant that is predicted to result in the substitution of tryptophan by leucine at amino acid 20 (p.Trp20Leu). To our knowledge, this variant has not been reported in individuals with GAMT deficiency and functional studies have not been performed. The computational predictor REVEL gives a score of 0.804 which is in the range of 0.773-0.932, evidence that correlates with impact to GAMT function at the moderate level (PMID: 36413997) (PP3_Moderate). Another missense variant, c.59G>C (p.Trp20Ser) (ClinVar Variation ID: 8303)) has been reported at the same amino acid position and has been classified as pathogenic for GAMT deficiency by the ClinGen CCDS VCEP (PM5). The highest population minor allele frequency in gnomAD v4.1.0. is 0.00005886 (4/67960 alleles) in the African / African-American population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 588631). In summary, this variant meets the criteria to be classified as uncertain significance 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): PM5, PP3_Moderate, PM2_Supporting (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on October 15, 2025)