FBXO7 c.122+343C>G
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 7.31%, mid) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +343 | deep intronic (+343 nt into the intron) |
|---|---|---|
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.98 | GERP -0.91, phastCons 0.001 |
| Overall | ||
| CADD | 1.999 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
7.31%
Middle Eastern · 437/5,982 alleles
Filtering AF
6.74%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.52%
Overall
1.97%
31,140/1,579,866 alleles · common
exomes 28,940/1,427,536 · genomes 2,200/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 7.31% | 14 |
| Ashkenazi Jewishnot grpmax-eligible | 4.66% | 21 |
| European (non-Finnish) | 2.18% | 46 |
| Remaining individualsnot grpmax-eligible | 2.1% | 48 |
| South Asian | 1.54% | 65 |
| Admixed American | 1.44% | 69 |
| Amishnot grpmax-eligible | 0.768% | 130 |
| Finnishnot grpmax-eligible | 0.537% | 186 |
| African / African-American | 0.45% | 222 |
| East Asian | 0.00233% | 42,848 |
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+343C>G
- MANE Select
- NM_012179
- dbSNP
- rs117106070
- Type
- single nucleotide variant
- Location
- chr22:32475467 (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-343c-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown