THOP1 p.His232=
c.696C>T · VCV4594900
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
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 -11 | GERP -3.3 |
| Overall | ||
| CADD | 3.815 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,080 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00294%
Overall
0.00422%
68/1,612,694 alleles · ultra-rare
exomes 64/1,460,476 · genomes 4/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,040 |
| East Asian | 0.00891% | 11,221 |
| South Asian | 0.00769% | 13,003 |
| European (non-Finnish) | 0.00424% | 23,597 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,226 |
| African / African-American | 0.00267% | 37,462 |
| Admixed American | 0.00167% | 59,952 |
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
- THOP1
- Protein
- p.His232=
- Coding
- c.696C>T
- MANE Select
- NM_003249
- Type
- single nucleotide variant
- Location
- chr19:2805122 (GRCh38)
- Gene constraint
- LOEUF 0.876 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.11 · 2 PDB
Similar variants
- THOP1 p.His232Tyr Uncertain significance ★ ⚠ same residue
- THOP1 p.Ala139Val Uncertain significance ★ ⚠ same type
- THOP1 p.Ala14Thr Uncertain significance ★ ⚠ same type
- THOP1 p.Ala292Val Uncertain significance ★ ⚠ same type
- THOP1 p.Ala299Val Uncertain significance ★ ⚠ same type
- THOP1 p.Ala319Val Uncertain significance ★ ⚠ same type
- THOP1 p.Ala387Thr Uncertain significance ★ ⚠ same type
- THOP1 p.Ala446Val 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/thop1-p-his232 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown