The NM_000156.6:c.444_448del (p.Phe149LeufsTer40) variant in GAMT is a frameshift variant that is predicted to cause a premature stop codon in the last 50 nucleotides of the penultimate exon of the gene and therefore to escape nonsense mediated decay. About 20% of the protein is predicted to be removed (PVS1_Strong). The variant is absent in gnomAD v4.1.0. (PM2_Supporting). One patient with clinical symptoms consistent with GAMT deficiency has been reported with elevated guanidinoacetate and low creatine in dried blood spot, and improvement in seizure frequency after 3 years of creatine treatment (PMID: 35588794) (PP4). This individual is compound heterozygous for the variant and another variant in GAMT that has been classified as likely pathogenic for GAMT deficiency by the CCDS VCEP, c.520T>C (p.Trp174Arg) (ClinVar Variation ID: 1420866), confirmed in trans by parental DNA testing (PMID: 35588794),1 point. (PM3). There is a ClinVar entry for this variant (Variation ID: 2831012). In summary, this variant meets the criteria to be classified as likely pathogenic for guanidinoacetate methyltransferase deficiency. GAMT-specific ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specification Version 2.0.0.): PVS1_Strong, PM3, PP4, PM2_Supporting (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on April 24, 2026)