F12 p.Gln520=
c.1560G>A · rs759021533 · VCV2656117
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.56 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 15.16 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
Middle Eastern · 2/5,278 alleles
Filtering AF
0.00845%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00662%
Overall
0.00143%
23/1,612,332 alleles · ultra-rare
exomes 23/1,459,974 · genomes 0/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0379% | 2,639 |
| South Asian | 0.0143% | 7,002 |
| Admixed American | 0.00833% | 12,006 |
| African / African-American | 0.00133% | 75,036 |
| European (non-Finnish) | 0.000169% | 590,012 |
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.Gln520=
- Coding
- c.1560G>A
- MANE Select
- NM_000505
- dbSNP
- rs759021533
- Type
- single nucleotide variant
- Location
- chr5:177402670 (GRCh38)
- Gene constraint
- LOEUF 1.286 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47 · 17 PDB
- Residue 520
- a β-strand; 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-gln520 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown