Is CBL p.Asn4= (c.12C>T) pathogenic?

CBL p.Asn4= (c.12C>T) is classified Benign/Likely benign in CBL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-27). Rare (popmax 0.13%, afr); Associated with Cardiovascular phenotype.

What condition is associated with CBL p.Asn4= (c.12C>T)?

CBL p.Asn4= (c.12C>T) is associated with Cardiovascular phenotype, juvenile myelomonocytic leukemia, RASopathy (ClinVar).

How common is CBL p.Asn4= (c.12C>T) in the general population?

CBL p.Asn4= (c.12C>T) is rare (popmax 0.13%, afr) (gnomAD).

CBL p.Asn4=

c.12C>T · rs371567712 · VCV179790

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.13%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.26	GERP -2.6, phastCons 0.29
Overall
CADD	11.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.13% African / African-American · 96/74,056 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.00765% 120/1,568,858 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.13%	771
East Asian	0.0185%	5,419
Remaining individualsnot grpmax-eligible	0.0115%	8,701
Admixed American	0.00733%	13,634
South Asian	0.00347%	28,811
European (non-Finnish)	0.000172%	581,301

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.Asn4=
Coding: c.12C>T
dbSNP: rs371567712
Type: single nucleotide variant
Location: chr11:119206429 (GRCh38)

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

Also linked: juvenile myelomonocytic leukemia RASopathy

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-asn4 (accessed [today's date]).

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