The NM_005629.4(SLC6A8):c.76G>A (p.Gly26Arg) variant in SLC6A8 is a missense variant predicted to cause substitution of Glycine for Arginine at amino acid 26 (p.Gly26Arg). In gnomAD v2.1.1, the highest population minor allele frequency is 0.0000257 (2/77768 alleles) in the European population, and there is 1 hemizygote present in this population database, therefore PM2_Supporting criteria is not met. The computational predictor REVEL gives a score of 0.079 which is below the threshold of 0.25, evidence and does not predict a damaging effect on SLC6A8 function. While functional studies were completed for the SLC6A8 c.76G>A (p.Gly26Arg) (PMID:17465020), they did not meet the specifications required for functional studies by the ClinGen Cerebral Creatine Deficiency Syndromes Variant Curation Expert Panel (<125uM Creatine used for transport assays). This variant has been reported in an individual in the literature (PMID:16738945), however biochemical evidence of Creatine Transport Deficiency (elevated urine creatine:creatinine) was not obtained for this individual, therefore it does not meet criteria established for PP4. There is a ClinVar entry for this variant (Variation ID:655315). In summary, this variant meets the criteria to be classified as a Variant of Uncertain Significance for Creatine Transporter 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): BP4. (Classification approved by the ClinGen CCDS VCEP on June 6, 2022).