TWF2 p.Pro342=
c.1026G>A · VCV3464588
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, amr)
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 |
|---|---|---|
| Pangolin | Δ0.71 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -4.4 |
| Overall | ||
| CADD | 0.039 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/60,002 alleles
Filtering AF
0.00773%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00579%
Overall
0.00149%
24/1,612,198 alleles · ultra-rare
exomes 19/1,459,830 · genomes 5/152,368 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,667 |
| African / African-American | 0.00533% | 18,756 |
| East Asian | 0.00223% | 44,882 |
| South Asian | 0.0022% | 45,499 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,360 |
| European (non-Finnish) | 0.000593% | 168,560 |
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
- TWF2
- Protein
- p.Pro342=
- Coding
- c.1026G>A
- MANE Select
- NM_007284
- Type
- single nucleotide variant
- Location
- chr3:52229058 (GRCh38)
- Gene constraint
- LOEUF 0.525 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 91.41 · 2 PDB
- Residue 342
- the 'disordered' region
Similar variants
- TWF2 p.Ala145Val Uncertain significance ★ ⚠ same type
- TWF2 p.Ala18Val Uncertain significance ★ ⚠ same type
- TWF2 p.Ala292Thr Uncertain significance ★ ⚠ same type
- TWF2 p.Ala87Thr Uncertain significance ★ ⚠ same type
- TWF2 p.Arg158Cys Uncertain significance ★ ⚠ same type
- TWF2 p.Arg188Trp Uncertain significance ★ ⚠ same type
- TWF2 p.Arg209Trp Uncertain significance ★ ⚠ same type
- TWF2 p.Arg231Gln 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/twf2-p-pro342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown