Is TOR1A p.Ser243= (c.729G>A) pathogenic?

TOR1A p.Ser243= (c.729G>A) is classified Likely benign in TOR1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-02). Ultra-rare (popmax 0.066%, mid); Associated with dystonic disorder.

What condition is associated with TOR1A p.Ser243= (c.729G>A)?

TOR1A p.Ser243= (c.729G>A) is associated with dystonic disorder (ClinVar).

How common is TOR1A p.Ser243= (c.729G>A) in the general population?

TOR1A p.Ser243= (c.729G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

TOR1A p.Ser243=

c.729G>A · rs753283496 · VCV2725206

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

dystonic disorder

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 -20	GERP -5.1
Overall
CADD	1.466	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00322% 47/1,461,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
European (non-Finnish)	0.00347%	28,781
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,086

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.Ser243=
Coding: c.729G>A
MANE Select: NM_000113
dbSNP: rs753283496
Type: single nucleotide variant
Location: chr9:129818539 (GRCh38)
Gene constraint: LOEUF 0.84 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.82 · 3 PDB
Residue 243: the 'interaction with snapin' region; a turn

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.Ser243Leu 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-ser243 (accessed [today's date]).

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