The NM_000156.6:c.22C>A variant in GAMT is a missense variant that is predicted to result in the substitution of proline by threonine at amino acid 8 (p.Pro8Thr). One patient, who is heterozygous for the variant, has been reported. This individual, who presented with severe global develpomental delay, hypotonia, and intractable seizures, died at 11 months of age. Urine and plasma guanidinoacetate were elevated 2.5 and 1.8 times, respectively. However, on 1H-MRS, creatine peak was about 90% of normal, marginally low, which was not suggestive of GAMT deficiency(PMID: 24415674) (PP4 not applied). GAA-deficient fibroblasts overexpressing the c.22C>A (p.Pro8Thr) variant showed similar GAMT enzyme activity as those transfected with wild-type cDNA (PMID: 24415674) (BS3_Supporting). The computational predictor REVEL gives a score of 0.479 which is below the threshold of 0.5, evidence that does not predict a damaging effect on GAMT function (BP4). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00023 (7/30820 alleles) in the European non-Finnish population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 205598). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for GAMT deficiency. GAMT-specific ACMG/AMP criteria met, based on the specifications of the ClinGen Cerebral Creatine Deficiencies VCEP (Specifications Version 1.1.0): BS3_Supporting, BP4, PM2_Supporting. Although this variant meets criteria for a classification of Variant of Uncertain Significance, the ClinGen Cerebral Creatine Deficiencies VCEP considers this variant suspicious for Likely Benign. Future literature may warrant a reclassification of this variant.