CBL p.Asp460del
c.1365TGA[5] · rs397507494 · VCV570415
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00606%, nfe)
Conditions
2
CBL-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 19.67 | PHRED · no single calibrated threshold — expert panels disagree |
| Region caveats | ||
| Repeat context | tandem | (ATG)n simple repeat · ambiguous alignment · confidence, not pathogenicity |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00606%
European (non-Finnish) · 71/1,171,750 alleles
Filtering AF
0.0049%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0045%
Overall
0.00505%
81/1,604,086 alleles · very rare
exomes 81/1,452,308 · genomes 0/151,778 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00606% | 16,504 |
| Remaining individualsnot grpmax-eligible | 0.00483% | 20,716 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,474 |
| South Asian | 0.0033% | 30,285 |
| Admixed American | 0.00167% | 59,856 |
| Finnishnot grpmax-eligible | 0.00157% | 63,702 |
| African / African-American | 0.00134% | 74,646 |
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.Asp460del
- Coding
- c.1365TGA[5]
- MANE Select
- NM_005188
- dbSNP
- rs397507494
- Type
- Microsatellite
- Location
- chr11:119278646 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
- Residue 460
- the 'required for ubiquitination of spred2' region; the 'disordered' region
Similar variants
- CBL p.Asp460dup Benign/Likely benign ★★ same residue
- CBL p.Asp460_Glu461insAspAsp Uncertain significance ★ same residue
- CBL p.Asp460= Likely benign ★★ same residue
- CBL p.His40_His42del Uncertain significance ★★ same condition
- CBL p.His41_His42del Uncertain significance ★★ same condition
- CBL p.Phe468fs Uncertain significance ★★ same condition
- CBL p.Ser799del Uncertain significance ★★ same condition
- CBL p.Thr811del Uncertain significance ★★ 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-asp460del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown