CBL p.Glu613Ter
c.1837G>T · rs2135310875 · VCV2720092
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
RASopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 16 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 40.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- CBL
- Protein
- p.Glu613Ter
- Coding
- c.1837G>T
- MANE Select
- NM_005188
- dbSNP
- rs2135310875
- Type
- single nucleotide variant
- Location
- chr11:119285462 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 64.27 · 34 PDB
- Residue 613
- the 'required for ubiquitination of spred2' region; the 'disordered' region
Similar variants
- CBL p.Glu613= Likely benign ★ 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-glu613ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown