FBXO7 c.418-2A>G
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function |
|---|---|---|
| Splicing | ||
| Splice region | acceptor -2 | canonical splice dinucleotide (acceptor -2) · inside the BP7-excluded zone |
| SpliceAI | Δ0.98 | acceptor loss · deltas |
| Pangolin | Δ0.86 | loss · gain 0.82 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2.7, phastCons 1 |
| Non-coding constraint | Z 1.73 | 1 kb window · o/e 0.87 · regional · uncalibrated |
| Overall | ||
| CADD | 35.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| European (non-Finnish)grpmax | 0.000339% | 294,850 |
Remaining individuals 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
- Coding
- c.418-2A>G
- MANE Select
- NM_012179
- dbSNP
- rs762209257
- Type
- single nucleotide variant
- Location
- chr22:32483895 (GRCh38)
- Gene constraint
- LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.13 · 2 PDB
Disease context
parkinsonian-pyramidal syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Parkinsonian-pyramidal syndrome (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adolescent, Adult
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-c-418-minus-2a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown