F12 p.Asn433=
c.1299C>T · rs17876033 · VCV352987
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.197%, nfe)
Conditions
1
hereditary angioedema type 3
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 2.5 | GERP -2.6, phastCons 1 |
| Overall | ||
| CADD | 9.801 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.197%
European (non-Finnish) · 2,316/1,178,438 alleles
Filtering AF
0.19%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.187%
Overall
0.156%
2,499/1,604,796 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.197% | 509 |
| Remaining individualsnot grpmax-eligible | 0.148% | 676 |
| Admixed American | 0.0924% | 1,083 |
| Middle Eastern | 0.0539% | 1,855 |
| African / African-American | 0.0387% | 2,583 |
| Finnishnot grpmax-eligible | 0.00509% | 19,632 |
| South Asian | 0.00111% | 90,290 |
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
- F12
- Protein
- p.Asn433=
- Coding
- c.1299C>T
- MANE Select
- NM_000505
- dbSNP
- rs17876033
- Type
- single nucleotide variant
- Location
- chr5:177403569 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 17 PDB
- Residue 433
- a disulfide bond; the peptidase s1 domain; a β-strand
Similar variants
- F12 p.Thr328Lys Pathogenic ★★ ⚠ same condition
- F12 c.1019-28T>C Benign ★★ same condition
- F12 c.1251-9C>T Benign/Likely benign ★★ same condition
- F12 c.1681-7G>A Benign/Likely benign ★★ same condition
- F12 c.398-12C>T Benign/Likely benign ★★ same condition
- F12 c.-4T>C Benign/Likely benign ★★ same condition
- F12 c.-8C>T Likely benign ★★ same condition
- F12 p.Ala207Pro Benign/Likely benign ★★ 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/f12-p-asn433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown