F11 p.Pro221=
c.663C>T · rs142846329 · VCV752344
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.416%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.255 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.3 | GERP -4.7 |
| Overall | ||
| CADD | 0.861 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.416%
African / African-American · 312/75,004 alleles
Filtering AF
0.378%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.363%
Overall
0.0229%
370/1,614,058 alleles · rare
exomes 203/1,461,888 · genomes 167/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.416% | 240 |
| Remaining individualsnot grpmax-eligible | 0.0416% | 2,404 |
| Admixed American | 0.015% | 6,667 |
| European (non-Finnish) | 0.00186% | 53,637 |
| South Asian | 0.0011% | 91,078 |
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
- F11
- Protein
- p.Pro221=
- Coding
- c.663C>T
- MANE Select
- NM_000128
- dbSNP
- rs142846329
- Type
- single nucleotide variant
- Location
- chr4:186276298 (GRCh38)
- Gene constraint
- LOEUF 1.145 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.94 · 117 PDB
- Residue 221
- the apple 3 domain
Similar variants
- F11 c.1136-1G>C Likely pathogenic ★★ same type
- F11 c.1480+1G>T Likely pathogenic ★★ same type
- F11 c.1481-1G>T Likely pathogenic ★★ same type
- F11 c.1716+1G>A Pathogenic ★★ same type
- F11 c.325+1G>A Pathogenic ★★ same type
- F11 c.326-1G>A Pathogenic ★★ same type
- F11 c.595+3A>G Pathogenic/Likely pathogenic ★★ same type
- F11 c.755+2T>C Pathogenic ★★ 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/f11-p-pro221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown