Is CBL p.Pro569del (c.1705_1707del) pathogenic?

CBL p.Pro569del (c.17051707del) is classified Uncertain significance in CBL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-17). Absent from gnomAD; Associated with CBL-related disorder.

What condition is associated with CBL p.Pro569del (c.1705_1707del)?

CBL p.Pro569del (c.1705_1707del) is associated with CBL-related disorder (ClinVar).

How common is CBL p.Pro569del (c.1705_1707del) in the general population?

CBL p.Pro569del (c.1705_1707del) is absent from gnomAD (gnomAD).

CBL p.Pro569del

c.1705_1707del · rs2135310558 · VCV1696266

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

CBL-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

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.Pro569del
Coding: c.1705_1707del
MANE Select: NM_005188
dbSNP: rs2135310558
Type: Deletion
Location: chr11:119285328 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 569: 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

CBL-related disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBL c.1096-4_1096-1del Pathogenic/Likely pathogenic ★★ same condition
CBL p.Gln367del Pathogenic/Likely pathogenic ★★ same condition
CBL c.2435-1_2435del Uncertain significance ★★ same condition
CBL p.Ile664fs Uncertain significance ★★ same condition
CBL p.Thr364del Likely pathogenic ★ same condition
CBL c.1227+2_1227+6del Uncertain significance ★ same condition
CBL p.Pro569Arg Uncertain significance ★ ⚠ same residue
CBL p.Pro569Leu Uncertain significance ★ same residue

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-pro569del (accessed [today's date]).

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