BBX p.Leu689=
c.2067G>A · rs201690465 · VCV3133189
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00967%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00967%
European (non-Finnish) · 114/1,179,440 alleles
Filtering AF
0.00818%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00761%
Overall
0.00762%
123/1,613,212 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00967% | 10,346 |
| Finnishnot grpmax-eligible | 0.00781% | 12,803 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,230 |
| African / African-American | 0.00267% | 37,462 |
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.Leu689=
- Coding
- c.2067G>A
- MANE Select
- NM_001142568
- dbSNP
- rs201690465
- Type
- single nucleotide variant
- Location
- chr3:107778383 (GRCh38)
- Gene constraint
- LOEUF 0.359 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 50.79
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-leu689 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown