CBL p.Pro782=
c.2346G>A · rs762655460 · VCV1096913
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
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 -9.6 | GERP -3.7 |
| Overall | ||
| CADD | 0.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,998 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.00105%
17/1,613,998 alleles · very rare
exomes 15/1,461,836 · genomes 2/152,162 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,998 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
| African / African-American | 0.00133% | 74,910 |
| European (non-Finnish) | 0.0011% | 90,769 |
| South Asian | 0.0011% | 91,078 |
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.Pro782=
- Coding
- c.2346G>A
- MANE Select
- NM_005188
- dbSNP
- rs762655460
- Type
- single nucleotide variant
- Location
- chr11:119298452 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
- Residue 782
- the 'required for ubiquitination of spred2' region; the 'interaction with cd2ap' region; a UniProt-annotated variant site (in)
Similar variants
- CBL p.Pro782Leu 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.1228-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Arg420Leu Likely pathogenic ★★ same condition
- CBL p.Gln367Arg Likely pathogenic ★★ same condition
- CBL p.Gln367Pro Pathogenic/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-pro782 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown