FBXO7 p.Gly512Asp
c.1535G>A · rs142471722 · VCV706329
Computational evidence
| Protein change | ||
| AlphaMissense | 0.2816 | likely benign |
|---|---|---|
| REVEL | 0.581 | indeterminate |
| SaProt | LLR -7.03 | tolerated |
| ⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 10 | GERP 2.6, phastCons 1 |
| Regional constraint | o/e 1.03 | unconstrained · MANE · 24 kb · p 0.42 · regional, not allelic |
| Overall | ||
| CADD | 26.4 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.22% | 455 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,676 |
| Finnishnot grpmax-eligible | 0.00156% | 63,904 |
| European (non-Finnish)grpmax | 0.000424% | 235,836 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- FBXO7
- Protein
- p.Gly512Asp
- Coding
- c.1535G>A
- MANE Select
- NM_012179
- dbSNP
- rs142471722
- Type
- single nucleotide variant
- Location
- chr22:32498496 (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 512
- the 'important for interaction with cdk6' region; the 'disordered' region
Similar variants
- FBXO7 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same condition
- FBXO7 p.Arg345Ter Pathogenic/Likely pathogenic ★★ same condition
- FBXO7 p.Arg381Ter Pathogenic/Likely pathogenic ★★ same condition
- FBXO7 p.Arg45Ter Pathogenic/Likely pathogenic ★★ same condition
- FBXO7 p.Arg498Ter Pathogenic ★★ same condition
- FBXO7 p.Gln237Ter Pathogenic/Likely pathogenic ★★ same condition
- FBXO7 p.Thr22Met Pathogenic/Likely pathogenic ★★ same condition
- FBXO7 p.Ala84Val Uncertain significance ★★ ⚠ 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/fbxo7-p-gly512asp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown