F8 p.Pro2240=
c.6720T>G · rs1395992838 · VCV2661861
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00123%, nfe)
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 0.73 | GERP -4, phastCons 0.99 |
| Overall | ||
| CADD | 7.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00123%
European (non-Finnish) · 11/895,014 alleles
Filtering AF
0.000659%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000482%
Overall
0.000909%
11/1,209,822 alleles · very rare
exomes 10/1,097,882 · genomes 1/111,940 · joint denominator
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
- F8
- Protein
- p.Pro2240=
- Coding
- c.6720T>G
- MANE Select
- NM_000132
- dbSNP
- rs1395992838
- Type
- single nucleotide variant
- Location
- chrX:154861721 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 2240
- the f5/8 type c 2 domain
Similar variants
- F8 p.Pro2240Leu Likely pathogenic ★ same residue
- F8 c.6429+2T>A Pathogenic ★★★ same type
- F8 p.Ala111Thr Likely pathogenic ★★★ same type
- F8 p.Ala2220Pro Pathogenic ★★★ same type
- F8 p.Ala415Asp Likely pathogenic ★★★ same type
- F8 p.Ala415Val Pathogenic ★★★ ⚠ same type
- F8 p.Arg1768His Pathogenic ★★★ ⚠ same type
- F8 p.Arg1800His 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/f8-p-pro2240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown