F7 p.Pro274=
c.822G>A · rs566083695 · VCV807055
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.336%, sas)
Conditions
1
factor VII deficiency
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 -3.5 | GERP -3.1 |
| Overall | ||
| CADD | 1.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.336%
South Asian · 306/91,052 alleles
Filtering AF
0.305%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.293%
Overall
0.0217%
350/1,610,394 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.336% | 298 |
| Middle Eastern | 0.0165% | 6,058 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,245 |
| African / African-American | 0.004% | 25,004 |
| Admixed American | 0.00333% | 30,007 |
| European (non-Finnish) | 0.00237% | 42,134 |
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
- F7
- Protein
- p.Pro274=
- Coding
- c.822G>A
- MANE Select
- NM_019616
- dbSNP
- rs566083695
- Type
- single nucleotide variant
- Location
- chr13:113118495 (GRCh38)
- Gene constraint
- LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.64 · 114 PDB
- Residue 274
- a β-strand; a disulfide bond; the peptidase s1 domain
Similar variants
- F7 p.Pro274Leu Uncertain significance ★ ⚠ same residue
- F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same condition
- F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same condition
- F7 c.-30A>C Likely pathogenic ★★ same condition
- F7 c.-55C>T Pathogenic/Likely pathogenic ★★ same condition
- F7 c.-61T>G Likely pathogenic ★★ same condition
- F7 p.Ala282Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- F7 p.Ala332Val Pathogenic/Likely pathogenic ★★ 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/f7-p-pro274 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown