Is CBL p.Ile885= (c.2655C>T) pathogenic?

CBL p.Ile885= (c.2655C>T) is classified Likely benign in CBL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). Ultra-rare (popmax 0.0165%, mid); Associated with Cardiovascular phenotype.

What condition is associated with CBL p.Ile885= (c.2655C>T)?

CBL p.Ile885= (c.2655C>T) is associated with Cardiovascular phenotype, RASopathy (ClinVar).

How common is CBL p.Ile885= (c.2655C>T) in the general population?

CBL p.Ile885= (c.2655C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

CBL p.Ile885=

c.2655C>T · rs747804658 · VCV1083180

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

Cardiovascular phenotype

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 -5.3	GERP -3.2
Overall
CADD	2.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000958% 14/1,461,892 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00333%	30,008
East Asian	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,084
European (non-Finnish)	0.000678%	147,504

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.Ile885=
Coding: c.2655C>T
MANE Select: NM_005188
dbSNP: rs747804658
Type: single nucleotide variant
Location: chr11:119299715 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 885: the 'required for ubiquitination of spred2' region; an α-helix; the 'interaction with cd2ap' region; the uba domain

Full CBL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: RASopathy

Similar variants

CBL p.Ile885Met Uncertain significance ★ ⚠ same residue
CBL p.Ile885Thr Uncertain significance ★★ ⚠ 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

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-ile885 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown