Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 66.4%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
CBL-related disorder
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 -0.28 | GERP -1.8 |
| Non-coding constraint | Z 3.20 | 1 kb window · o/e 0.78 · regional · uncalibrated |
| Overall | ||
| CADD | 0.356 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
66.4%
African / African-American · 30,050/45,278 alleles
Filtering AF
65.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 65.5%
Overall
38.3%
89,072/232,766 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 66.4% | 2 |
| East Asian | 40.4% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 37.9% | 3 |
| Remaining individualsnot grpmax-eligible | 35.9% | 3 |
| Middle Eastern | 35.1% | 3 |
| Finnishnot grpmax-eligible | 31.4% | 3 |
| European (non-Finnish) | 30.2% | 3 |
| Admixed American | 29% | 3 |
| Amishnot grpmax-eligible | 26.2% | 4 |
| South Asian | 22.9% | 4 |
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
- Coding
- c.*4584C>A
- MANE Select
- NM_005188
- dbSNP
- rs2509671
- Type
- single nucleotide variant
- Location
- chr11:119304365 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
Similar variants
- 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
- CBL p.Gln367Pro Pathogenic/Likely pathogenic ★★ same condition
- CBL p.Tyr371Asn 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-c-star-4584c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown