BBX p.Pro759=
c.2277C>T · rs200449835 · VCV713780
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.19%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.438 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 10.15 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.19%
European (non-Finnish) · 2,177/1,145,480 alleles
Filtering AF
0.183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.181%
Overall
0.149%
2,304/1,549,536 alleles · rare
exomes 2,200/1,397,336 · genomes 104/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.19% | 526 |
| Remaining individualsnot grpmax-eligible | 0.18% | 556 |
| African / African-American | 0.0205% | 4,871 |
| Admixed American | 0.00393% | 25,468 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0035% | 28,602 |
| Finnishnot grpmax-eligible | 0.00167% | 59,800 |
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
- BBX
- Protein
- p.Pro759=
- Coding
- c.2277C>T
- MANE Select
- NM_001142568
- dbSNP
- rs200449835
- Type
- single nucleotide variant
- Location
- chr3:107789860 (GRCh38)
- Gene constraint
- LOEUF 0.359 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 50.79
- Residue 759
- the 'disordered' region
Similar variants
- BBX p.Ala442Thr Benign ★★ same type
- BBX p.Ala60= Likely benign ★★ same type
- BBX p.Ala892= Benign ★★ same type
- BBX p.Ala139Thr Uncertain significance ★ ⚠ same type
- BBX p.Ala143Gly Uncertain significance ★ ⚠ same type
- BBX p.Ala269Pro Uncertain significance ★ ⚠ same type
- BBX p.Ala354Thr Uncertain significance ★ ⚠ same type
- BBX p.Ala375Thr 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/bbx-p-pro759 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown