F8 p.Ser899Asn
c.2696G>A · rs145089334 · VCV913257
ClinGen expert panel — Coagulation Factor Deficiency VCEP
Likely Benign for hemophilia A. Applied ACMG criteria (verbatim):
BS1 BP4
Curation rationale (ClinGen, verbatim)
The c.2696G>A (p.Ser899Asn) is a missense variant is reported in gnomAD v4.1 with a Gprmax FAF = 0.00009278, meeting BS1 criteria of greater than or equal to 0.00333% (or 0.0000333). The variant has a REVEL score of 0.234 (<0.3) and a SpliceAI score of 0.0 meeting BP4. In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Coagulation Factor Deficiency Variant Curation Expert Panel for F8 v2.0: BS1 and BP4.
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1011 | likely benign |
|---|---|---|
| REVEL | 0.234 | benign-leaning |
| SaProt | LLR -6.86 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.046 | GERP -2.7, phastCons 0.002 |
| Regional constraint | o/e 0.99 | unconstrained · MANE · 2,842 bp · p 0.74 · regional, not allelic |
| Overall | ||
| CADD | 3.502 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0111% | 9,021 |
| East Asian | 0.00888% | 11,259 |
| Remaining individualsnot grpmax-eligible | 0.00633% | 15,797 |
| African / African-American | 0.00351% | 28,514 |
| Admixed American | 0.00222% | 45,112 |
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.Ser899Asn
- Coding
- c.2696G>A
- MANE Select
- NM_000132
- dbSNP
- rs145089334
- Type
- single nucleotide variant
- Location
- chrX:154931094 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 899
- the 'b' region
Disease context
hemophilia A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Hemophilia A (Orphanet):
- Inheritance
- X-linked recessive
- Onset
- Childhood, Infancy, Neonatal
- Prevalence
- 1-9 / 100 000 (Worldwide)
Similar variants
- F8 c.6429+2T>A Pathogenic ★★★ same condition
- F8 p.Ala111Thr Likely pathogenic ★★★ same condition
- F8 p.Ala2220Pro Pathogenic ★★★ same condition
- F8 p.Ala415Asp Likely pathogenic ★★★ same condition
- F8 p.Ala415Val Pathogenic ★★★ ⚠ same condition
- F8 p.Arg1768His Pathogenic ★★★ ⚠ same condition
- F8 p.Arg1800His Pathogenic ★★★ same condition
- F8 p.Arg2016Trp 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/f8-p-ser899asn (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown