The NM_000156.6:c.564G>T variant in GAMT is a missense variant predicted to cause substitution of methionine by isoleucine at amino acid 188 (p.Met188Ile). This variant has been detected in Chinese individual with elevated guanidinoacetate and low creatine in both serum and urine, and a significantly reduced peak of creatine on brain MRS; full GAMT gene sequencing done (PP4_Strong) (PMID: 28438604). This patient was 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.491dupG. The variants were confirmed to be in trans by parental testing (PMID: 28438604) (1 point) (PM3). The variant is absent in gnomAD v4.1.0. (PM2_Supporting). The computational predictor REVEL gives a score of 0.735 which is in the range of 0.644-0.773, evidence that correlates with impact to GAMT function at the supporting level (PP3). There is a ClinVar entry for this variant (Variation ID: 2570636). 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): PP4_Strong, PM3, PP3, PM2_Supporting (Classification approved by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel on October 15, 2025)