Is SLC6A8 p.Pro37= (c.111C>G) pathogenic?

SLC6A8 p.Pro37= (c.111C>G) is classified Likely benign in SLC6A8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Very rare (popmax 0.0039%, afr); Associated with creatine transporter deficiency.

What condition is associated with SLC6A8 p.Pro37= (c.111C>G)?

SLC6A8 p.Pro37= (c.111C>G) is associated with creatine transporter deficiency (ClinVar).

How common is SLC6A8 p.Pro37= (c.111C>G) in the general population?

SLC6A8 p.Pro37= (c.111C>G) is very rare (popmax 0.0039%, afr) (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.Pro37=

c.111C>G · rs1165376297 · VCV3010100

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0039%, afr)

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 -0.41	GERP -2.5
Overall
CADD	7.967	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0039% African / African-American · 2/51,271 alleles

Filtering AF 0.000647% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000242%

Overall 0.000181% 2/1,102,056 alleles · very rare exomes 0/993,314 · genomes 2/108,742 · joint denominator

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.Pro37=
Coding: c.111C>G
MANE Select: NM_005629
dbSNP: rs1165376297
Type: single nucleotide variant
Location: chrX:153688685 (GRCh38)
Structure: AlphaFold pLDDT 85.63 · 6 PDB

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 p.Pro37Ser Uncertain significance ★ ⚠ same residue
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

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-pro37 (accessed [today's date]).

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