F8 p.Ala2347Pro
c.7039G>C · VCV4685784
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1913 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1913 | likely benign |
|---|---|---|
| REVEL | 0.664 | pathogenic-leaning |
| SaProt | LLR -6.07 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.18 | GERP -3.4 |
| Regional constraint | o/e 0.65 | unconstrained · MANE · 91 kb · p 1.5e-14 · regional, not allelic |
| Overall | ||
| CADD | 10.55 | 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.Ala2347Pro
- Coding
- c.7039G>C
- MANE Select
- NM_000132
- Type
- single nucleotide variant
- Location
- chrX:154837614 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
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-ala2347pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown