Is CBL p.Pro510Ser (c.1527_1528delinsCT) pathogenic?

CBL p.Pro510Ser (c.15271528delinsCT) is classified Uncertain significance in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). No gnomAD frequency available for this variant; Associated with RASopathy.

What condition is associated with CBL p.Pro510Ser (c.1527_1528delinsCT)?

CBL p.Pro510Ser (c.1527_1528delinsCT) is associated with RASopathy (ClinVar).

How common is CBL p.Pro510Ser (c.1527_1528delinsCT) in the general population?

CBL p.Pro510Ser (c.1527_1528delinsCT) is no gnomAD frequency available for this variant (gnomAD).

CBL p.Pro510Ser

c.1527_1528delinsCT · rs2496951660 · VCV2990422

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 0.29	GERP 0.87, phastCons 0.05
Regional constraint	o/e 1.05	unconstrained · MANE · 22 kb · p 0.19 · 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.Pro510Ser
Coding: c.1527_1528delinsCT
MANE Select: NM_005188
dbSNP: rs2496951660
Type: Indel
Location: chr11:119285064 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 510: the 'required for ubiquitination of spred2' 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.Pro510Arg Uncertain significance ★★ ⚠ same residue
CBL p.Pro510= Likely benign ★★ same residue
CBL p.Pro510Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-pro510ser (accessed [today's date]).

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