F5 p.Val427=
c.1281C>G · rs1292267151 · VCV3051731
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.80 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.57 | gain · loss 0.30 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 8.6 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 20.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,600 alleles
Overall
6.84e-05%
1/1,461,240 alleles · very rare
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
- F5
- Protein
- p.Val427=
- Coding
- c.1281C>G
- MANE Select
- NM_000130
- dbSNP
- rs1292267151
- Type
- single nucleotide variant
- Location
- chr1:169552572 (GRCh38)
- Gene constraint
- LOEUF 0.704 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 62.57 · 23 PDB
- Residue 427
- the f5/8 type a 2 domain; the plastocyanin-like 3 domain
Similar variants
- F5 c.1297-2A>G Pathogenic/Likely pathogenic ★★ same type
- F5 p.Arg1030Ter Pathogenic ★★ same type
- F5 p.Arg146Ter Pathogenic/Likely pathogenic ★★ same type
- F5 p.Arg1621Ter Pathogenic/Likely pathogenic ★★ same type
- F5 p.Arg1634Ter Pathogenic/Likely pathogenic ★★ same type
- F5 p.Arg2102His Pathogenic/Likely pathogenic ★★ same type
- F5 p.Arg740Ter Pathogenic/Likely pathogenic ★★ same type
- F5 p.Asp96His 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/f5-p-val427 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown