Is THAP1 p.Met1fs (c.2del) pathogenic?

THAP1 p.Met1fs (c.2del) is classified Pathogenic/Likely pathogenic in THAP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). No gnomAD frequency available for this variant; Associated with torsion dystonia 6.

What condition is associated with THAP1 p.Met1fs (c.2del)?

THAP1 p.Met1fs (c.2del) is associated with torsion dystonia 6 (ClinVar).

How common is THAP1 p.Met1fs (c.2del) in the general population?

THAP1 p.Met1fs (c.2del) 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.Met1fs

c.2del · rs2487042330 · VCV1711673

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 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 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, 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.Met1fs
Coding: c.2del
MANE Select: NM_018105
dbSNP: rs2487042330
Type: Deletion
Location: chr8:42843093 (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.Met1Leu Pathogenic ★ same residue
THAP1 p.Met1Thr Pathogenic ★ same residue
THAP1 p.Met1Val Pathogenic ★ same residue
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

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-met1fs (accessed [today's date]).

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