The NM_000156.6:c.233T>A variant in GAMT is a missense variant predicted to cause substitution of valine by glutamic acid at amino acid 78 (p.Val78Glu). This variant has been detected in two siblings with GAMT deficiency from one family (PMID: 23660394, PMID: 24268530, PMID: 24071436). The proband showed elevated guanidinoacetate and low creatine in plasma, elevated urine guanidinoacetate, and low creatine peak on brain MRS (PMID: 24071436) (PP4_Strong). These individuals were reported to be 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.299_311dup13 (p.Arg105GfsTer26) (ClinVar Variation ID: 8302); the variants were confirmed to be in trans (PMID: 23660394, PMID: 24268530, PMID: 24071436) (1pt) (PM3). The highest population minor allele frequency in gnomAD v4.1.0. is 0.0000016 (2/1178172 alleles) in the non-Finnish European population, which is lower than the ClinGen CCDS VCEP’s threshold for PM2_Supporting (<0.0004), meeting this criterion (PM2_Supporting). The computational predictor REVEL gives a score of 0.794 which is above the threshold of 0.75, evidence that correlates with impact to GAMT function (PP3). There is no ClinVar entry for this variant. 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 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)