THAP1 p.Thr165=
c.495C>T · rs140668058 · VCV1555272
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.012%, afr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -4.6 |
| Overall | ||
| CADD | 1.683 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.012%
African / African-American · 9/74,908 alleles
Filtering AF
0.00624%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00468%
Overall
0.00149%
24/1,614,022 alleles · ultra-rare
exomes 18/1,461,884 · genomes 6/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.012% | 8,323 |
| Admixed American | 0.00167% | 59,990 |
| European (non-Finnish) | 0.00119% | 84,289 |
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.Thr165=
- Coding
- c.495C>T
- MANE Select
- NM_018105
- dbSNP
- rs140668058
- Type
- single nucleotide variant
- Location
- chr8:42838109 (GRCh38)
- Gene constraint
- LOEUF 0.571 · pLI 0.90 (gnomAD)
- Structure
- AlphaFold pLDDT 71.61 · 3 PDB
- Residue 165
- the 'involved in homodimer formation' region
Similar variants
- 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
- THAP1 p.Arg169Gln Uncertain significance ★★ ⚠ 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-thr165 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown