FBXO7 c.122+555A>G
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +555 | deep intronic (+555 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.8 | GERP -1.9 |
| Overall | ||
| CADD | 0.124 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.02%
African / African-American · 1,448/47,894 alleles
Filtering AF
2.89%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.84%
Overall
0.401%
1,660/414,052 alleles · low-frequency
exomes 260/261,718 · genomes 1,400/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.02% | 33 |
| Admixed American | 0.422% | 237 |
| Remaining individualsnot grpmax-eligible | 0.322% | 311 |
| Middle Eastern | 0.319% | 313 |
| European (non-Finnish) | 0.02% | 5,003 |
| South Asian | 0.017% | 5,883 |
| Finnishnot grpmax-eligible | 0.0167% | 5,981 |
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+555A>G
- MANE Select
- NM_012179
- dbSNP
- rs79971293
- Type
- single nucleotide variant
- Location
- chr22:32475679 (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-555a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown