F12 p.Ser495=
c.1485C>G · rs113304533 · VCV3025588
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00933%, 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 -3.4 | GERP -3.9 |
| Overall | ||
| CADD | 3.495 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00933%
African / African-American · 7/75,024 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.00075%
12/1,599,892 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00933% | 10,718 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,802 |
| South Asian | 0.0011% | 91,068 |
| European (non-Finnish) | 8.48e-05% | 1,179,807 |
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.Ser495=
- Coding
- c.1485C>G
- MANE Select
- NM_000505
- dbSNP
- rs113304533
- Type
- single nucleotide variant
- Location
- chr5:177403300 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 17 PDB
- Residue 495
- the peptidase s1 domain
Similar variants
- 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
- F12 p.Gly360Val 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-ser495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown