F12 p.Ser533=
c.1599A>G · rs1424350386 · VCV983443
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, 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 -1.6 | GERP -4.6 |
| Overall | ||
| CADD | 3.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,022 alleles
Overall
0.000657%
1/152,234 alleles · very rare
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.Ser533=
- Coding
- c.1599A>G
- MANE Select
- NM_000505
- dbSNP
- rs1424350386
- Type
- single nucleotide variant
- Location
- chr5:177402631 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 17 PDB
- Residue 533
- a disulfide bond; the peptidase s1 domain
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-ser533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown