The NM_000156.6:595dupG (p.Glu199GlyfsTer68) variant in GAMT is a frameshift variant predicted to cause a premature stop codon in the last exon of the gene and therefore to escape nonsense mediated decay. Less than 10% of the protein is predicted to be removed (PVS1_Moderate). This variant has been detected in one individual with an absent creatine peak on brain MRS and low plasma creatine (PMID: 32606525) (PP4_Moderate). This individual was homozygous for the variant (PMID: 32606525) (0.5pts, PM3_Supporting). This individual had an absent creatine peak on brain MRS (PMID: 32606525) (PP4_Moderate). This variant is absent in gnomAD v4.1.0. (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 2570639). 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): PVS1_Moderate, PM2_Supporting, PM3_Supporting, PP4_Moderate. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on October 7, 2025)