CBL p.Pro453=
c.1359A>C · rs34732429 · VCV162834
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 13 submitters
gnomAD v4.1
Rare
rare (popmax 0.615%, afr)
Conditions
4
Cardiovascular phenotype
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 0.16 | GERP -4.2, phastCons 0.14 |
| Overall | ||
| CADD | 7.909 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.615%
African / African-American · 461/75,010 alleles
Filtering AF
0.568%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.55%
Overall
0.0351%
567/1,614,100 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.615% | 163 |
| Remaining individualsnot grpmax-eligible | 0.0848% | 1,179 |
| Admixed American | 0.075% | 1,333 |
| Middle Eastern | 0.0495% | 2,021 |
| European (non-Finnish) | 0.000424% | 236,003 |
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
- CBL
- Protein
- p.Pro453=
- Coding
- c.1359A>C
- MANE Select
- NM_005188
- dbSNP
- rs34732429
- Type
- single nucleotide variant
- Location
- chr11:119278641 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
- Residue 453
- the 'required for ubiquitination of spred2' region; the 'disordered' region
Similar variants
- CBL p.Pro453Leu Uncertain significance ★★ ⚠ same residue
- CBL p.Pro453Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- CBL c.1096-1G>C Pathogenic/Likely pathogenic ★★ same condition
- CBL c.1096-1G>T Pathogenic ★★ same condition
- CBL c.1096-2A>T Pathogenic ★★ same condition
- CBL c.1228-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Arg420Leu Likely pathogenic ★★ same condition
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/cbl-p-pro453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown