Is CBL p.Gln490fs (c.1466dup) pathogenic?

CBL p.Gln490fs (c.1466dup) is classified Uncertain significance in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). Absent from gnomAD; Associated with RASopathy.

What condition is associated with CBL p.Gln490fs (c.1466dup)?

CBL p.Gln490fs (c.1466dup) is associated with RASopathy (ClinVar).

How common is CBL p.Gln490fs (c.1466dup) in the general population?

CBL p.Gln490fs (c.1466dup) is absent from gnomAD (gnomAD).

CBL p.Gln490fs

c.1466dup · rs2496951420 · VCV2810213

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

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 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 0.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBL
Protein: p.Gln490fs
Coding: c.1466dup
MANE Select: NM_005188
dbSNP: rs2496951420
Type: Duplication
Location: chr11:119284999 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 490: the 'required for ubiquitination of spred2' region; the 'disordered' region

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

Disease context

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

Similar variants

CBL p.Gln490Glu Uncertain significance ★★ ⚠ same residue
CBL p.Leu43_Ser44insHisHisLeu Uncertain significance ★★ same condition
CBL p.Leu805_Asp806insVal Uncertain significance ★★ same condition
CBL p.Ser858_Ser859insLeuSer Uncertain significance ★★ same condition
CBL c.1227+20dup Benign/Likely benign ★★ same condition
CBL c.1228-10dup Benign/Likely benign ★★ same condition
CBL c.2434+15dup Likely benign ★★ same condition
CBL c.1007+2dup 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-gln490fs (accessed [today's date]).

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