FBXO7 c.122+382G>A
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.75%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +382 | deep intronic (+382 nt into the intron) |
|---|---|---|
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.81 | GERP -1.8, phastCons 0.002 |
| Overall | ||
| CADD | 2.333 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.75%
African / African-American · 1,212/69,128 alleles
Filtering AF
1.67%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.64%
Overall
0.111%
1,587/1,425,198 alleles · low-frequency
exomes 802/1,272,836 · genomes 785/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.75% | 57 |
| Admixed American | 0.287% | 348 |
| Middle Eastern | 0.264% | 379 |
| Remaining individualsnot grpmax-eligible | 0.182% | 548 |
| South Asian | 0.0308% | 3,243 |
| European (non-Finnish) | 0.0086% | 11,626 |
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.122+382G>A
- MANE Select
- NM_012179
- dbSNP
- rs150339020
- Type
- single nucleotide variant
- Location
- chr22:32475506 (GRCh38)
- Gene constraint
- LOEUF 0.955 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 67.13 · 2 PDB
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-c-122-plus-382g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown