The NM_000156.6:c.526del (p.Glu176SerfsTer2) variant in GAMT is a frameshift variant predicted to cause a premature stop codon in the last 50 nucleotides of the penultimate exon/the last exon of the gene and therefore to escape nonsense mediated decay. More than 10% of the protein is predicted to be removed (PVS1_Strong). This variant in not in gnomAD v2.1.1 (PM2_Supporting). This variant has been reported in one individual with GAMT deficiency who had elevated GAA and low creatine in plasma and in urine (PMID: 19288536) (PP4_Moderate). There is a ClinVar entry for this variant (Variation ID: 1067935, 1 star review status) with 1 submitter classifying the variant as likely pathogenic. In summary, this variant meets the criteria to be classified as likely pathogenic for GAMT deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (Specifications Version 1.1.0): PVS1_Strong, PM2_Supporting, PP4_Moderate. (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on April 13, 2023)