Is TOR1A p.Ile24= (c.72C>T) pathogenic?

TOR1A p.Ile24= (c.72C>T) is classified Conflicting classifications of pathogenicity in TOR1A (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-04-25). Very rare (popmax 0.00695%, nfe); Associated with dystonic disorder.

What condition is associated with TOR1A p.Ile24= (c.72C>T)?

TOR1A p.Ile24= (c.72C>T) is associated with dystonic disorder (ClinVar).

How common is TOR1A p.Ile24= (c.72C>T) in the general population?

TOR1A p.Ile24= (c.72C>T) is very rare (popmax 0.00695%, nfe) (gnomAD).

TOR1A p.Ile24=

c.72C>T · rs762152420 · VCV624371

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00695%, nfe)

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 3.6	GERP 1.5, phastCons 1
Overall
CADD	15.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% European (non-Finnish) · 82/1,179,214 alleles

Filtering AF 0.00571% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00534% 86/1,610,126 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00695%	14,381
East Asian	0.00223%	44,800
Admixed American	0.00167%	59,884
Remaining individualsnot grpmax-eligible	0.00161%	62,222
African / African-American	0.00134%	74,884

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.Ile24=
Coding: c.72C>T
MANE Select: NM_000113
dbSNP: rs762152420
Type: single nucleotide variant
Location: chr9:129824014 (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.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
TOR1A p.Leu179Phe 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-ile24 (accessed [today's date]).

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