Is TOR1A p.Ser57Arg (c.171C>G) pathogenic?

TOR1A p.Ser57Arg (c.171C>G) is classified Uncertain significance in TOR1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: ambiguous (0.3493); Very rare (popmax 6.94e-05%); Associated with dystonic disorder.

What condition is associated with TOR1A p.Ser57Arg (c.171C>G)?

TOR1A p.Ser57Arg (c.171C>G) is associated with dystonic disorder (ClinVar).

How common is TOR1A p.Ser57Arg (c.171C>G) in the general population?

TOR1A p.Ser57Arg (c.171C>G) is very rare (popmax 6.94e-05%) (gnomAD).

What do computational predictors say about TOR1A p.Ser57Arg (c.171C>G)?

AlphaMissense predicts ambiguous (score 0.3493) — an in-silico prediction, not a clinical call.

TOR1A p.Ser57Arg

c.171C>G · rs990435438 · VCV1720217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3493 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.94e-05%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.3493	ambiguous
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.38	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 10 kb · p 0.042 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.94e-05%

Overall 6.94e-05% 1/1,440,072 alleles · very rare

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.Ser57Arg
Coding: c.171C>G
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.Ser57= Likely benign ★ 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-ser57arg (accessed [today's date]).

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