Is THAP1 p.Phe45fs (c.135_139delinsGGGTTTA) pathogenic?

THAP1 p.Phe45fs (c.135139delinsGGGTTTA) is classified Pathogenic in THAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-22). No gnomAD frequency available for this variant; Associated with torsion dystonia 6.

What condition is associated with THAP1 p.Phe45fs (c.135_139delinsGGGTTTA)?

THAP1 p.Phe45fs (c.135_139delinsGGGTTTA) is associated with torsion dystonia 6 (ClinVar).

How common is THAP1 p.Phe45fs (c.135_139delinsGGGTTTA) in the general population?

THAP1 p.Phe45fs (c.135_139delinsGGGTTTA) is no gnomAD frequency available for this variant (gnomAD).

How is Primary dystonia, DYT6 type inherited?

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

THAP1 p.Phe45fs

c.135_139delinsGGGTTTA · rs1586457060 · VCV817036

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

torsion dystonia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: THAP1
Protein: p.Phe45fs
Coding: c.135_139delinsGGGTTTA
MANE Select: NM_018105
dbSNP: rs1586457060
Type: Indel
Location: chr8:42839314 (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.Phe45Cys Pathogenic ★ same residue
THAP1 p.Phe45= Likely benign ★ same residue
THAP1 c.72-10_72-9delinsGC Uncertain significance ★ same condition
THAP1 c.270_273del Pathogenic/Likely pathogenic ★★ same condition
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.Asn69del Pathogenic/Likely pathogenic ★★ 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-phe45fs (accessed [today's date]).

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