Is SLC6A3 p.Ser321= (c.963C>T) pathogenic?

SLC6A3 p.Ser321= (c.963C>T) is classified Likely benign in SLC6A3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). Absent from gnomAD v4.1; Associated with parkinsonism-dystonia, infantile.

What condition is associated with SLC6A3 p.Ser321= (c.963C>T)?

SLC6A3 p.Ser321= (c.963C>T) is associated with parkinsonism-dystonia, infantile (ClinVar).

How common is SLC6A3 p.Ser321= (c.963C>T) in the general population?

SLC6A3 p.Ser321= (c.963C>T) is absent from gnomAD v4.1 (gnomAD).

How is Infantile dystonia-parkinsonism inherited?

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

SLC6A3 p.Ser321=

c.963C>T · rs2477359988 · VCV2025976

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -3.9	GERP -4.8
Overall
CADD	4.662	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: SLC6A3
Protein: p.Ser321=
Coding: c.963C>T
MANE Select: NM_001044
dbSNP: rs2477359988
Type: single nucleotide variant
Location: chr5:1416166 (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 321: a binding site; 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

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-ser321 (accessed [today's date]).

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