CBLB p.Pro689=
c.2067G>A · rs34801525 · VCV774844
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.83%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.29 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.37 | gain · loss 0.25 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -2 | GERP -3.6 |
| Overall | ||
| CADD | 12.78 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.83%
Middle Eastern · 111/6,058 alleles
Filtering AF
1.56%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.45%
Overall
0.677%
10,917/1,612,824 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.83% | 55 |
| Ashkenazi Jewishnot grpmax-eligible | 1.15% | 87 |
| European (non-Finnish) | 0.791% | 126 |
| Remaining individualsnot grpmax-eligible | 0.68% | 147 |
| Admixed American | 0.573% | 174 |
| South Asian | 0.239% | 418 |
| African / African-American | 0.147% | 682 |
| Finnishnot grpmax-eligible | 0.0594% | 1,684 |
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
- CBLB
- Protein
- p.Pro689=
- Coding
- c.2067G>A
- MANE Select
- NM_170662
- dbSNP
- rs34801525
- Type
- single nucleotide variant
- Location
- chr3:105685454 (GRCh38)
- Gene constraint
- LOEUF 0.406 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 62.88 · 36 PDB
- Residue 689
- the 'disordered' region; a UniProt-annotated variant site (in admio3; likely pathogenic)
Similar variants
- CBLB p.Arg670Gln Benign/Likely benign ★★ same type
- CBLB p.Pro387= Benign ★★ same type
- CBLB p.Ser622Thr Benign/Likely benign ★★ same type
- CBLB c.2569+1609A>C Uncertain significance ★ same type
- CBLB p.Ala176Pro Uncertain significance ★ ⚠ same type
- CBLB p.Ala2Glu Uncertain significance ★ ⚠ same type
- CBLB p.Ala592Ser Uncertain significance ★ ⚠ same type
- CBLB p.Ala928Val 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/cblb-p-pro689 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown