Is SLC6A8 p.Ala2= (c.6G>A) pathogenic?

SLC6A8 p.Ala2= (c.6G>A) is classified Likely benign in SLC6A8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-09). Very rare (popmax 0.0005%, nfe); Associated with creatine transporter deficiency.

What condition is associated with SLC6A8 p.Ala2= (c.6G>A)?

SLC6A8 p.Ala2= (c.6G>A) is associated with creatine transporter deficiency (ClinVar).

How common is SLC6A8 p.Ala2= (c.6G>A) in the general population?

SLC6A8 p.Ala2= (c.6G>A) is very rare (popmax 0.0005%, nfe) (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.Ala2=

c.6G>A · rs1557043713 · VCV2064955

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0005%, nfe)

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 2.4	GERP -0.89, phastCons 1
Overall
CADD	13.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0005% European (non-Finnish) · 4/800,498 alleles

Filtering AF 0.000117% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.9e-05%

Overall 0.000484% 5/1,032,024 alleles · very rare exomes 4/927,550 · genomes 1/104,474 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00261%	38,323
European (non-Finnish)grpmax	0.0005%	200,124

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SLC6A8
Protein: p.Ala2=
Coding: c.6G>A
MANE Select: NM_005629
dbSNP: rs1557043713
Type: single nucleotide variant
Location: chrX:153688580 (GRCh38)
Structure: AlphaFold pLDDT 85.63 · 6 PDB
Residue 2: the 'disordered' region

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-ala2 (accessed [today's date]).

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