CBL p.Glu220=
c.660G>A · rs949933368 · VCV1338196
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000848%, nfe)
Conditions
2
RASopathy
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 1.3 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 6.738 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000848%
European (non-Finnish) · 10/1,179,862 alleles
Filtering AF
0.000429%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000313%
Overall
0.00062%
10/1,613,856 alleles · very rare
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.Glu220=
- Coding
- c.660G>A
- MANE Select
- NM_005188
- dbSNP
- rs949933368
- Type
- single nucleotide variant
- 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 220
- the cbl-ptb domain; the 'sufficient for interaction with ephb1' region; the 'ef-hand-like' region; an α-helix
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.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-glu220 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown