The NM_000156.6:c.134G>A (p.Trp45Ter) variant in GAMT is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 1/6 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant has been detected in at least two probands with GAMT deficiency. Of those probands, both were homozygous for the variant (PMIDs 31222513, 33996490) (PM3). At least one proband (two siblings) with this variant had elevated GAA and low creatine in plasma (PP4). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 2419155). In summary, this variant meets the criteria to be classified as 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, PM3, PP4, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP on Oct 12, 2023)