Is THAP1 p.Arg29Gln (c.86G>A) pathogenic?

THAP1 p.Arg29Gln (c.86G>A) is classified Likely pathogenic in THAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-16). AlphaMissense: likely pathogenic (0.8333); Very rare (popmax 0.00223%, eas).

How common is THAP1 p.Arg29Gln (c.86G>A) in the general population?

THAP1 p.Arg29Gln (c.86G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about THAP1 p.Arg29Gln (c.86G>A)?

AlphaMissense predicts likely pathogenic (score 0.8333) — an in-silico prediction, not a clinical call.

THAP1 p.Arg29Gln

c.86G>A · rs767952378 · VCV2684079

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8333	likely pathogenic ✓ concordant with ClinVar
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 5,129 bp · p 1.3e-06 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,842 alleles

Overall 0.000248% 4/1,613,794 alleles · very rare exomes 4/1,461,666 · genomes 0/152,128 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,598
East Asiangrpmax	0.00223%	44,842
Remaining individualsnot grpmax-eligible	0.0016%	62,496
European (non-Finnish)	8.47e-05%	1,179,972

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg29Gln
Coding: c.86G>A
MANE Select: NM_018105
dbSNP: rs767952378
Type: single nucleotide variant
Location: chr8:42839367 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 71.61 · 3 PDB
Residue 29: a UniProt-annotated variant site (in dyt6)

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

Similar variants

THAP1 p.Arg29Pro Pathogenic/Likely pathogenic ★★ same residue
THAP1 p.Arg29Ter Pathogenic/Likely pathogenic ★★ same residue
THAP1 p.Arg29Gly Likely pathogenic ★ same residue
THAP1 p.Arg169Ter Pathogenic/Likely pathogenic ★★ same type
THAP1 p.Gly9Ser Likely pathogenic ★★ same type
THAP1 p.Pro26Leu Pathogenic/Likely pathogenic ★★ same type
THAP1 p.Ser130Ter Pathogenic/Likely pathogenic ★★ same type
THAP1 p.Ser21Phe Likely pathogenic ★★ same type

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-arg29gln (accessed [today's date]).

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