Is THAP1 c.71+9C>A pathogenic?

THAP1 c.71+9C>A is classified Benign/Likely benign in THAP1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2025-12-19). Rare (popmax 0.214%, nfe); Associated with torsion dystonia 6.

What condition is associated with THAP1 c.71+9C>A?

THAP1 c.71+9C>A is associated with torsion dystonia 6 (ClinVar).

How common is THAP1 c.71+9C>A in the general population?

THAP1 c.71+9C>A is rare (popmax 0.214%, nfe) (gnomAD).

How is Primary dystonia, DYT6 type inherited?

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

THAP1 c.71+9C>A

rs200209986 · VCV363126

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.214%, nfe)

Conditions

torsion dystonia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 0.049
Non-coding constraint	Z -0.57	1 kb window · o/e 1.04 · regional · uncalibrated
Overall
CADD	11.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% European (non-Finnish) · 2,518/1,178,248 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.174% 2,802/1,610,816 alleles · rare exomes 2,621/1,458,674 · genomes 181/152,142 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.214%	468
Admixed American	0.132%	758
Remaining individualsnot grpmax-eligible	0.13%	769
South Asian	0.0913%	1,095
Middle Eastern	0.0333%	3,007
African / African-American	0.0307%	3,257
Finnishnot grpmax-eligible	0.0252%	3,974

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: THAP1
Coding: c.71+9C>A
MANE Select: NM_018105
dbSNP: rs200209986
Type: single nucleotide variant
Location: chr8:42843015 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 71.61 · 3 PDB

Full THAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

torsion dystonia 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Primary dystonia, DYT6 type (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

THAP1 p.Arg169Ter Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Arg29Pro Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Arg29Ter Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Gly9Ser Likely pathogenic ★★ same condition
THAP1 p.Pro26Leu Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Ser130Ter Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Ser21Phe Likely pathogenic ★★ same condition
THAP1 p.Arg169Gln 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/thap1-c-71-plus-9c-a (accessed [today's date]).

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