CBL p.Ala221fs
c.661del · VCV4733706
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 4 of 16 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 9.2 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- CBL
- Protein
- p.Ala221fs
- Coding
- c.661del
- MANE Select
- NM_005188
- Type
- Deletion
- Location
- chr11:119273937 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
- Residue 221
- the cbl-ptb domain; the 'sufficient for interaction with ephb1' region; the 'ef-hand-like' region; an α-helix
Similar variants
- CBL c.1096-4_1096-1del Pathogenic/Likely pathogenic ★★ same condition
- CBL c.2435-1_2435del Uncertain significance ★★ same condition
- CBL p.Ile664fs Uncertain significance ★★ same condition
- CBL c.1096-9del Likely benign ★★ same condition
- CBL c.1228-20_1228-17del Benign/Likely benign ★★ same condition
- CBL c.1432-12del Benign/Likely benign ★★ same condition
- CBL c.2251+14_2251+22del Benign/Likely benign ★★ same condition
- CBL c.870-19del Benign/Likely benign ★★ 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-ala221fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown