The NM_000156.6:c.439C>T variant in GAMT is predicted to result in the substitution of histidine by tyrosine at amino acid 147 (p.His147Tyr). This variant has been identified in an individual with a diagnosis of guanidinoacetate methyltransferase deficiency confirmed by deficient enzyme activity in cultured fibroblasts (PMID: 24415674) (PP4_Moderate). 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.11_36dup (p.Gly13fs) (ClinVar Variation ID: 858462); the phase is unconfirmed (PMID: 24415674) (0.5 points) (PM3_Supporting). The highest population minor allele frequency in gnomAD v4.1.0. is 0.00001335 (1/74918 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). This variant was shown to result in 4% of wild-type enzyme activity in GAMT-deficient fibroblasts (PMID: 24415674) (PS3_Supporting). The computational predictor REVEL gives a score of 0.888 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). There is a ClinVar entry for this variant (Variation ID: 2446460). In summary, this variant meets criteria to be classified as likely pathogenic for guanidinoacetate methyltransferase (GAMT) deficiency. GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiencies Variant Curation Expert Panel (CCDS VCEP) (Specifications version 2.0.0): PP3_Moderate, PP4_Moderate, PS3_Supporting, PM2_Supporting, PM3_Supporting (Classification approved by the ClinGen Cerebral Creatine Deficiencies Variant Curation Expert Panel on October 15, 2025)