Is SLC6A3 p.Phe362= (c.1086C>T) pathogenic?

SLC6A3 p.Phe362= (c.1086C>T) is classified Benign/Likely benign in SLC6A3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-15). Rare (popmax 0.377%, amr); Associated with parkinsonism-dystonia, infantile.

What condition is associated with SLC6A3 p.Phe362= (c.1086C>T)?

SLC6A3 p.Phe362= (c.1086C>T) is associated with parkinsonism-dystonia, infantile (ClinVar).

How common is SLC6A3 p.Phe362= (c.1086C>T) in the general population?

SLC6A3 p.Phe362= (c.1086C>T) is rare (popmax 0.377%, amr) (gnomAD).

How is Infantile dystonia-parkinsonism inherited?

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

SLC6A3 p.Phe362=

c.1086C>T · rs28363072 · VCV695829

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.377%, amr)

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 -1.4	GERP -4.9
Overall
CADD	8.867	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.377% Admixed American · 226/60,008 alleles

Filtering AF 0.336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.321%

Overall 0.0259% 418/1,612,920 alleles · rare exomes 378/1,460,690 · genomes 40/152,230 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.377%	266
East Asian	0.0245%	4,081
South Asian	0.0231%	4,337
Remaining individualsnot grpmax-eligible	0.0144%	6,942
European (non-Finnish)	0.0119%	8,428
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
African / African-American	0.00667%	15,000
Finnishnot grpmax-eligible	0.00635%	15,751

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.Phe362=
Coding: c.1086C>T
MANE Select: NM_001044
dbSNP: rs28363072
Type: single nucleotide variant
Location: chr5:1414761 (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 362: 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 p.Phe362Leu 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-phe362 (accessed [today's date]).

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