Is SLC6A8 p.Phe488= (c.1464T>C) pathogenic?

SLC6A8 p.Phe488= (c.1464T>C) is classified Likely benign in SLC6A8 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-20). Absent from gnomAD v4.1; Associated with creatine transporter deficiency.

What condition is associated with SLC6A8 p.Phe488= (c.1464T>C)?

SLC6A8 p.Phe488= (c.1464T>C) is associated with creatine transporter deficiency (ClinVar).

How common is SLC6A8 p.Phe488= (c.1464T>C) in the general population?

SLC6A8 p.Phe488= (c.1464T>C) is absent from gnomAD v4.1 (gnomAD).

How is X-linked creatine transporter deficiency inherited?

Typically Not applicable, X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SLC6A8 p.Phe488=

c.1464T>C · VCV4754986

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

creatine transporter deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.664	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.2	GERP -3.4, phastCons 0.85
Overall
CADD	8.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SLC6A8
Protein: p.Phe488=
Coding: c.1464T>C
MANE Select: NM_005629
Type: single nucleotide variant
Location: chrX:153694415 (GRCh38)
Structure: AlphaFold pLDDT 85.63 · 6 PDB
Residue 488: an α-helix

Full SLC6A8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

creatine transporter deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked creatine transporter deficiency (Orphanet):

Inheritance: Not applicable, X-linked recessive
Onset: Childhood, Infancy

Similar variants

SLC6A8 c.1016+2T>C Pathogenic ★★★ same condition
SLC6A8 c.1142-2A>G Likely pathogenic ★★★ same condition
SLC6A8 c.1495+2T>G Pathogenic ★★★ same condition
SLC6A8 c.1495+5G>C Pathogenic ★★★ same condition
SLC6A8 c.262+1G>T Pathogenic ★★★ same condition
SLC6A8 c.263-1G>C Pathogenic ★★★ same condition
SLC6A8 c.263-2A>G Pathogenic ★★★ same condition
SLC6A8 c.778-2A>G Likely pathogenic ★★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/slc6a8-p-phe488 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown