The NM_005629.4:c.1421A>G variant in SLC6A8 is a missense variant that is predicted to result in the substitution of aspartate by glycine at amino acid 474 (p.Asp474Gly). This variant has been reported in one (hemizygous) male proband with mild intellectual disability, elevated urine creatine/creatinine, and absent creatine peak on brain MRS (PMID: 29435807) (PP4_Strong). The variant is absent in gnomAD v2.1.1. (PM2_Supporting). The computational predictor REVEL gives a score of 0.971 which is above the threshold of 0.75, evidence that correlates with impact to SLC6A8 function (PP3). There is no ClinVar entry for this variant. In summary, this variant meets criteria to be classified as likely pathogenic for creatine transporter deficiency. SLC6A8-specific criteria applied, as specified by the ClinGen CCDS VCEP (Specifications Version 1.1.0): PP4_Strong, PP3, PM2_Supporting. (Classification approved by the ClinGen CCDS VCEP, August 7, 2023)