FBXO7 p.Gly245Val
c.734G>T · VCV4530906
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.168 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.168 | likely benign |
|---|---|---|
| REVEL | 0.239 | benign-leaning |
| SaProt | LLR -11.55 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense and REVEL do not. | ||
| Splicing | ||
| SpliceAI | Δ0.92 | donor gain · deltas |
| Pangolin | Δ0.66 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 3.2 | GERP 0.47, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 26.7 | 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
- FBXO7
- Protein
- p.Gly245Val
- Coding
- c.734G>T
- MANE Select
- NM_012179
- Type
- single nucleotide variant
- Location
- chr22:32485156 (GRCh38)
- Gene constraint
- LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.13 · 2 PDB
- Residue 245
- the 'important for dimerization and interaction with psmf1' region
Similar variants
- FBXO7 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same type
- FBXO7 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same type
- FBXO7 p.Arg381Ter Pathogenic/Likely pathogenic ★★ same type
- FBXO7 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same type
- FBXO7 p.Arg498Ter Pathogenic ★★ same type
- FBXO7 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same type
- FBXO7 p.Thr22Met Pathogenic/Likely pathogenic ★★ same type
- FBXO7 p.Ala84Val Uncertain significance ★★ ⚠ 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/fbxo7-p-gly245val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown