F8 p.Val727Phe
c.2179G>T · VCV3766796
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.7948 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.7948 | likely pathogenic ✓ concordant with ClinVar · top 10% in F8 |
|---|---|---|
| REVEL | 0.906 | moderately pathogenic-leaning |
| SaProt | LLR -14.45 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.7, phastCons 1 |
| Regional constraint | o/e 0.74 | unconstrained · MANE · 38 kb · p 2.6e-06 · regional, not allelic |
| Overall | ||
| CADD | 25.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Val727Phe
- Coding
- c.2179G>T
- MANE Select
- NM_000132
- Type
- single nucleotide variant
- Location
- chrX:154931611 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 727
- the plastocyanin-like 4 domain; a UniProt-annotated variant site (in hema; severe); a disulfide bond; a β-strand; the f5/8 type a 2 domain
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-val727phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown