F12 p.Ser479=
c.1437G>T · rs145585290 · VCV2414519
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.31%, afr)
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 -1.2 | GERP -3.3 |
| Overall | ||
| CADD | 14.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.31%
African / African-American · 233/75,042 alleles
Filtering AF
0.278%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.265%
Overall
0.025%
400/1,599,082 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.31% | 322 |
| Remaining individualsnot grpmax-eligible | 0.0305% | 3,283 |
| Admixed American | 0.025% | 3,998 |
| European (non-Finnish) | 0.0113% | 8,869 |
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.Ser479=
- Coding
- c.1437G>T
- MANE Select
- NM_000505
- dbSNP
- rs145585290
- Type
- single nucleotide variant
- Location
- chr5:177403348 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 17 PDB
- Residue 479
- a disulfide bond; the peptidase s1 domain
Similar variants
- F12 p.Ser479Pro Uncertain significance ★★ ⚠ same residue
- F12 p.Glu193Ter Pathogenic/Likely pathogenic ★★ same type
- F12 p.Thr328Lys Pathogenic ★★ ⚠ same type
- F12 c.57+4A>G Uncertain significance ★★ same type
- F12 p.Ala452Thr Uncertain significance ★★ ⚠ same type
- F12 p.Arg55Trp Uncertain significance ★★ ⚠ same type
- F12 p.Asp283= Uncertain significance ★★ same type
- F12 p.Glu288Lys 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/f12-p-ser479 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown