Is TOR1A p.Ser57= (c.171C>T) pathogenic?

TOR1A p.Ser57= (c.171C>T) is classified Likely benign in TOR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-10). Very rare (popmax 0.00404%, afr); Associated with dystonic disorder.

What condition is associated with TOR1A p.Ser57= (c.171C>T)?

TOR1A p.Ser57= (c.171C>T) is associated with dystonic disorder (ClinVar).

How common is TOR1A p.Ser57= (c.171C>T) in the general population?

TOR1A p.Ser57= (c.171C>T) is very rare (popmax 0.00404%, afr) (gnomAD).

TOR1A p.Ser57=

c.171C>T · rs990435438 · VCV2738407

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00404%, afr)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Overall
CADD	15.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00404% African / African-American · 3/74,246 alleles

Filtering AF 0.00107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000498%

Overall 0.000377% 6/1,591,606 alleles · very rare exomes 5/1,440,070 · genomes 1/151,536 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00404%	24,749
East Asian	0.0023%	43,502
Remaining individualsnot grpmax-eligible	0.00162%	61,578
South Asian	0.00113%	88,178

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: TOR1A
Protein: p.Ser57=
Coding: c.171C>T
MANE Select: NM_000113
dbSNP: rs990435438
Type: single nucleotide variant
Location: chr9:129823915 (GRCh38)
Gene constraint: LOEUF 0.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.82 · 3 PDB

Full TOR1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TOR1A p.Ser57Arg Uncertain significance ★ ⚠ same residue
TOR1A p.Arg288Ter Pathogenic/Likely pathogenic ★★ same condition
TOR1A p.Ala239Thr Uncertain significance ★★ ⚠ same condition
TOR1A p.Ala239Val Uncertain significance ★★ ⚠ same condition
TOR1A p.Arg213Gly Uncertain significance ★★ ⚠ same condition
TOR1A p.Arg260Trp Uncertain significance ★★ ⚠ same condition
TOR1A p.Asp331Asn Uncertain significance ★★ ⚠ same condition
TOR1A p.Cys44Gly 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/tor1a-p-ser57 (accessed [today's date]).

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