THAP1 p.Ala39=
c.117T>C · rs1586457076 · VCV784772
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00549%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.79 | GERP 1.2 |
| Overall | ||
| CADD | 9.984 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00549%
South Asian · 5/91,084 alleles
Filtering AF
0.0021%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000372%
6/1,614,060 alleles · very rare
exomes 6/1,461,742 · genomes 0/152,318 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00549% | 18,217 |
| European (non-Finnish) | 8.47e-05% | 1,179,997 |
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.Ala39=
- Coding
- c.117T>C
- MANE Select
- NM_018105
- dbSNP
- rs1586457076
- Type
- single nucleotide variant
- Location
- chr8:42839336 (GRCh38)
- Gene constraint
- LOEUF 0.571 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 71.61 · 3 PDB
- Residue 39
- an α-helix; a UniProt-annotated variant site (in dyt6)
Similar variants
- THAP1 p.Arg169Ter Pathogenic/Likely pathogenic ★★ same type
- THAP1 p.Arg29Pro Pathogenic/Likely pathogenic ★★ same type
- THAP1 p.Arg29Ter 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
- THAP1 p.Arg169Gln Uncertain significance ★★ ⚠ 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-ala39 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown