Is SLC6A3 p.Asp381= (c.1143C>T) pathogenic?

SLC6A3 p.Asp381= (c.1143C>T) is classified Likely benign in SLC6A3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0867%, sas); Associated with parkinsonism-dystonia, infantile.

What condition is associated with SLC6A3 p.Asp381= (c.1143C>T)?

SLC6A3 p.Asp381= (c.1143C>T) is associated with parkinsonism-dystonia, infantile, classic dopamine transporter deficiency syndrome, tobacco addiction, susceptibility to (ClinVar).

How common is SLC6A3 p.Asp381= (c.1143C>T) in the general population?

SLC6A3 p.Asp381= (c.1143C>T) is ultra-rare (popmax 0.0867%, sas) (gnomAD).

How is Infantile dystonia-parkinsonism inherited?

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

SLC6A3 p.Asp381=

c.1143C>T · rs8179027 · VCV696815

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0867%, sas)

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 -4.9	GERP -4.7
Overall
CADD	1.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0867% South Asian · 79/91,080 alleles

Filtering AF 0.0713% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0657%

Overall 0.0243% 392/1,612,492 alleles · ultra-rare exomes 366/1,460,338 · genomes 26/152,154 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0867%	1,153
East Asian	0.0847%	1,181
African / African-American	0.028%	3,569
European (non-Finnish)	0.0189%	5,291
Remaining individualsnot grpmax-eligible	0.0176%	5,679
Middle Eastern	0.0166%	6,034
Finnishnot grpmax-eligible	0.0159%	6,280
Admixed American	0.015%	6,665

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.Asp381=
Coding: c.1143C>T
MANE Select: NM_001044
dbSNP: rs8179027
Type: single nucleotide variant
Location: chr5:1414704 (GRCh38)
Gene constraint: LOEUF 0.393 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.58 · 12 PDB
Residue 381: an α-helix

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

Also linked: classic dopamine transporter deficiency syndrome tobacco addiction, susceptibility to

For Infantile dystonia-parkinsonism (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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
SLC6A3 p.Arg610His 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-asp381 (accessed [today's date]).

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