Is CBL p.Pro250= (c.750C>G) pathogenic?

CBL p.Pro250= (c.750C>G) is classified Likely benign in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-30). Very rare (popmax 6.2e-05%); Associated with Cardiovascular phenotype.

What condition is associated with CBL p.Pro250= (c.750C>G)?

CBL p.Pro250= (c.750C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is CBL p.Pro250= (c.750C>G) in the general population?

CBL p.Pro250= (c.750C>G) is very rare (popmax 6.2e-05%) (gnomAD).

CBL p.Pro250=

c.750C>G · VCV4613886

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

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 -0.79	GERP -3.8, phastCons 0.004
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,660 alleles · very rare exomes 1/1,461,514 · genomes 0/152,146 · joint denominator

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.Pro250=
Coding: c.750C>G
MANE Select: NM_005188
Type: single nucleotide variant
Location: chr11:119274834 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 250: the cbl-ptb domain; the 'sufficient for interaction with ephb1' region; the 'sh2-like' region

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

Similar variants

CBL p.Ala187Ser Uncertain significance ★★ ⚠ same condition
CBL p.Ala187Val Uncertain significance ★★ ⚠ same condition
CBL p.Ala208Thr Uncertain significance ★★ ⚠ same condition
CBL p.Ala385Gly Uncertain significance ★★ ⚠ same condition
CBL p.Ala450Val Uncertain significance ★★ ⚠ same condition
CBL p.Ala513Thr Uncertain significance ★★ ⚠ same condition
CBL p.Ala556Gly Uncertain significance ★★ ⚠ same condition
CBL p.Ala672Asp 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-pro250 (accessed [today's date]).

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