Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 73.1%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
parkinsonian-pyramidal syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.37, phastCons 1 |
| Overall | ||
| CADD | 10.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
73.1%
East Asian · 32,726/44,768 alleles
Filtering AF
72.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 72.2%
Overall
40.3%
648,192/1,606,990 alleles · common
exomes 584,951/1,455,106 · genomes 63,241/151,884 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 73.1% | 1 |
| Admixed American | 57.2% | 2 |
| Finnishnot grpmax-eligible | 47.3% | 2 |
| South Asian | 46.6% | 2 |
| Middle Eastern | 42.2% | 2 |
| Remaining individualsnot grpmax-eligible | 41.5% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 40.8% | 2 |
| African / African-American | 38.3% | 3 |
| European (non-Finnish) | 37.4% | 3 |
| Amishnot grpmax-eligible | 34.7% | 3 |
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.Leu317=
- Coding
- c.949C>T
- MANE Select
- NM_012179
- dbSNP
- rs9726
- Type
- single nucleotide variant
- Location
- chr22:32491163 (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 317
- an α-helix; the 'important for dimerization and interaction with psmf1' region
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-p-leu317 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown