F8 p.Lys2091=
c.6273G>A · rs2148584915 · VCV1330691
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hemophilia A
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.81 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.74 | loss · gain 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 21.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- F8
- Protein
- p.Lys2091=
- Coding
- c.6273G>A
- MANE Select
- NM_000132
- dbSNP
- rs2148584915
- Type
- single nucleotide variant
- Location
- chrX:154899866 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 2091
- the f5/8 type c 1 domain; a β-strand
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 p.Lys2091Asn Likely pathogenic ★ ⚠ same residue
- 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
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-lys2091 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown