Is SLC6A8 p.Ala559= (c.1677C>T) pathogenic?

SLC6A8 p.Ala559= (c.1677C>T) is classified Likely benign in SLC6A8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-09-24). Absent from gnomAD v4.1; Associated with creatine transporter deficiency.

What condition is associated with SLC6A8 p.Ala559= (c.1677C>T)?

SLC6A8 p.Ala559= (c.1677C>T) is associated with creatine transporter deficiency (ClinVar).

How common is SLC6A8 p.Ala559= (c.1677C>T) in the general population?

SLC6A8 p.Ala559= (c.1677C>T) 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.Ala559=

c.1677C>T · rs1057522460 · VCV386244

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.52	GERP 1.9
Overall
CADD	8.916	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.Ala559=
Coding: c.1677C>T
MANE Select: NM_005629
dbSNP: rs1057522460
Type: single nucleotide variant
Location: chrX:153694799 (GRCh38)
Structure: AlphaFold pLDDT 85.63 · 6 PDB
Residue 559: 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-ala559 (accessed [today's date]).

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