The NM_005629.4(SLC6A8):c.92C>T variant in SLC6A8 is a missense variant predicted to cause substitution of Proline for Leucine at amino acid 31 (p.Pro31Leu). In gnomAD v2.1.1, the highest population minor allele frequency is 0.0001300 (4/30763 alleles) in the European population with 1 hemizygote, which is >0.0002 and >1 hemizygote, therefore PM2_Supporting criteria is not applicable. The computational predictor REVEL gives a score of 0.114 which is below the threshold of 0.25, and does not predict a damaging effect on SLC6A8 function, and SpliceAI predicts no impact on splicing. This variant has been reported in a single individual in the literature (PMID:31222513) in a proband (case 1) with seizures, neurological regression, and spasticity who was found by WES to be hemizygous for the c.92C>T (p.Pro31Leu) variant, however biochemical studies were not performed to confirm creatine transporter deficiency, therefore this proband cannot be used as evidence for SLC6A8 variant classification. There is a ClinVar entry for this variant (Variation ID:572616). 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).