Is SLC6A3 p.Pro236= (c.708G>A) pathogenic?

SLC6A3 p.Pro236= (c.708G>A) is classified Likely benign in SLC6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-24). Very rare (popmax 0.00267%, afr); Associated with parkinsonism-dystonia, infantile.

What condition is associated with SLC6A3 p.Pro236= (c.708G>A)?

SLC6A3 p.Pro236= (c.708G>A) is associated with parkinsonism-dystonia, infantile (ClinVar).

How common is SLC6A3 p.Pro236= (c.708G>A) in the general population?

SLC6A3 p.Pro236= (c.708G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Infantile dystonia-parkinsonism inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SLC6A3 p.Pro236=

c.708G>A · rs1002810411 · VCV2867051

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

parkinsonism-dystonia, infantile

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 -1.8	GERP -4.9
Overall
CADD	7.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,932 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00112% 18/1,613,048 alleles · very rare exomes 15/1,460,840 · genomes 3/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,466
East Asian	0.00223%	44,898
Finnishnot grpmax-eligible	0.00159%	63,030
European (non-Finnish)	0.00119%	84,287

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: SLC6A3
Protein: p.Pro236=
Coding: c.708G>A
MANE Select: NM_001044
dbSNP: rs1002810411
Type: single nucleotide variant
Location: chr5:1421960 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.58 · 12 PDB

Full SLC6A3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

parkinsonism-dystonia, infantile — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile dystonia-parkinsonism (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SLC6A3 p.Pro236Leu Uncertain significance ★★ ⚠ same residue
SLC6A3 c.1269+1G>A Pathogenic ★★ same condition
SLC6A3 p.Ala308Val Uncertain significance ★★ ⚠ same condition
SLC6A3 p.Ala346Val Uncertain significance ★★ ⚠ same condition
SLC6A3 p.Ala565Ser Uncertain significance ★★ ⚠ same condition
SLC6A3 p.Arg304Gln Uncertain significance ★★ ⚠ same condition
SLC6A3 p.Arg51Gln Uncertain significance ★★ ⚠ same condition
SLC6A3 p.Arg588Gln Uncertain significance ★★ ⚠ 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/slc6a3-p-pro236 (accessed [today's date]).

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