FBXO7 c.1182+173T>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 46.1%, eas) — 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 +173 | deep intronic (+173 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1 | GERP 0.42, phastCons 0.93 |
| Non-coding constraint | Z 0.35 | 1 kb window · o/e 0.97 · regional · uncalibrated |
| Overall | ||
| CADD | 4.864 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
46.1%
East Asian · 2,383/5,172 alleles
Filtering AF
44.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 43.9%
Overall
13%
19,829/152,176 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 46.1% | 2 |
| South Asian | 25.8% | 4 |
| Admixed American | 20.4% | 5 |
| African / African-American | 15.9% | 6 |
| Finnishnot grpmax-eligible | 14.7% | 7 |
| Middle Eastern | 13.3% | 8 |
| Remaining individualsnot grpmax-eligible | 13% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 10.1% | 10 |
| Amishnot grpmax-eligible | 7.57% | 13 |
| European (non-Finnish) | 6.21% | 16 |
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.1182+173T>C
- MANE Select
- NM_012179
- dbSNP
- rs5749452
- Type
- single nucleotide variant
- Location
- chr22:32495703 (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-1182-plus-173t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown