Is CBL p.Ser15Pro (c.43_44delinsCC) pathogenic?

CBL p.Ser15Pro (c.4344delinsCC) is classified Uncertain significance in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). No gnomAD frequency available for this variant; Associated with RASopathy.

What condition is associated with CBL p.Ser15Pro (c.43_44delinsCC)?

CBL p.Ser15Pro (c.43_44delinsCC) is associated with RASopathy (ClinVar).

How common is CBL p.Ser15Pro (c.43_44delinsCC) in the general population?

CBL p.Ser15Pro (c.43_44delinsCC) is no gnomAD frequency available for this variant (gnomAD).

CBL p.Ser15Pro

c.43_44delinsCC · rs1555225091 · VCV543972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.97, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 26 kb · p 0.76 · regional, not allelic

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.Ser15Pro
Coding: c.43_44delinsCC
MANE Select: NM_005188
dbSNP: rs1555225091
Type: Indel
Location: chr11:119206460 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 15: the 'sufficient for interaction with ephb1' 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 c.195+12_195+13delinsTT Likely benign ★★ same condition
CBL c.1227+2_1227+4delinsAAG Pathogenic ★ same condition
CBL c.1095+18_1095+19delinsGT Conflicting classifications of pathogenicity ★ same condition
CBL c.1228-4_1228-3delinsCT Uncertain significance ★ same condition
CBL p.Leu637His Uncertain significance ★ same condition
CBL p.Pro510Ser Uncertain significance ★ same condition
CBL p.Ser15Arg Uncertain significance ★ ⚠ same residue
CBL p.Ser15Thr 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-ser15pro (accessed [today's date]).

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