Is THAP1 p.Asp15del (c.43_45del) pathogenic?

THAP1 p.Asp15del (c.4345del) is classified Conflicting classifications of pathogenicity in THAP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-16). Very rare (popmax 0.00133%, afr); Associated with torsion dystonia 6.

What condition is associated with THAP1 p.Asp15del (c.43_45del)?

THAP1 p.Asp15del (c.43_45del) is associated with torsion dystonia 6 (ClinVar).

How common is THAP1 p.Asp15del (c.43_45del) in the general population?

THAP1 p.Asp15del (c.43_45del) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Primary dystonia, DYT6 type inherited?

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

THAP1 p.Asp15del

c.43_45del · rs1478723907 · VCV567899

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 0.00133%, afr)

Conditions

torsion dystonia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.1	GERP 1.9, phastCons 1
Overall
CADD	19.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,922 alleles

Overall 6.2e-05% 1/1,613,790 alleles · very rare exomes 0/1,461,630 · genomes 1/152,160 · joint denominator

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
Protein: p.Asp15del
Coding: c.43_45del
MANE Select: NM_018105
dbSNP: rs1478723907
Type: Deletion
Location: chr8:42843050 (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.Met1fs Pathogenic/Likely pathogenic ★★ same condition
THAP1 p.Ala38fs Pathogenic ★ same condition
THAP1 p.Asn44fs Pathogenic ★ same condition
THAP1 p.Ile116fs Pathogenic ★ same condition
THAP1 p.Lys24fs Pathogenic ★ same condition
THAP1 p.Lys64fs Likely pathogenic ★ same condition
THAP1 p.Ser130fs Likely pathogenic ★ same condition
THAP1 c.268-53_386del Conflicting classifications of pathogenicity ★ 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-p-asp15del (accessed [today's date]).

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