F8 p.Pro909=
c.2727A>G · rs782300219 · VCV2661869
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, mid)
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 -0.018 | GERP -3.2, phastCons 0.017 |
| Overall | ||
| CADD | 1.407 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
Middle Eastern · 1/4,283 alleles
Filtering AF
0.00353%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00235%
Overall
0.0023%
25/1,085,827 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0233% | 4,283 |
| South Asian | 0.0092% | 10,872 |
| European (non-Finnish) | 0.00214% | 46,820 |
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.Pro909=
- Coding
- c.2727A>G
- MANE Select
- NM_000132
- dbSNP
- rs782300219
- Type
- single nucleotide variant
- Location
- chrX:154931063 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 909
- the 'b' region; the 'disordered' region
Similar variants
- 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
- F8 p.Arg2016Trp 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-pro909 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown