Is THAP1 p.Pro106= (c.318G>A) pathogenic?

THAP1 p.Pro106= (c.318G>A) is classified Likely benign in THAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-06). Rare (popmax 0.132%, mid); Associated with torsion dystonia 6.

What condition is associated with THAP1 p.Pro106= (c.318G>A)?

THAP1 p.Pro106= (c.318G>A) is associated with torsion dystonia 6 (ClinVar).

How common is THAP1 p.Pro106= (c.318G>A) in the general population?

THAP1 p.Pro106= (c.318G>A) is rare (popmax 0.132%, mid) (gnomAD).

How is Primary dystonia, DYT6 type inherited?

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

THAP1 p.Pro106=

c.318G>A · rs189728728 · VCV2741690

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

torsion dystonia 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.241	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.2	GERP -4.6
Overall
CADD	6.376	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,060 alleles

Filtering AF 0.0657% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0479%

Overall 0.0039% 63/1,613,948 alleles · rare exomes 54/1,461,734 · genomes 9/152,214 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	758
East Asian	0.0735%	1,360
African / African-American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0016%	62,496
European (non-Finnish)	0.00127%	78,661
South Asian	0.0011%	91,066

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.Pro106=
Coding: c.318G>A
MANE Select: NM_018105
dbSNP: rs189728728
Type: single nucleotide variant
Location: chr8:42838286 (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.Pro106Ser Uncertain significance ★ ⚠ same residue
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

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-pro106 (accessed [today's date]).

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