Is CBL p.Tyr371= (c.1113C>T) pathogenic?

CBL p.Tyr371= (c.1113C>T) is classified Likely benign in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-16). Very rare (popmax 0.00223%, eas); Associated with Cardiovascular phenotype.

What condition is associated with CBL p.Tyr371= (c.1113C>T)?

CBL p.Tyr371= (c.1113C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is CBL p.Tyr371= (c.1113C>T) in the general population?

CBL p.Tyr371= (c.1113C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CBL p.Tyr371=

c.1113C>T · rs1949904161 · VCV2567298

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 2.2	GERP 0.37, phastCons 1
Overall
CADD	9.667	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,832 alleles

Overall 0.000125% 2/1,599,886 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,832
European (non-Finnish)	8.57e-05%	1,167,302

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.Tyr371=
Coding: c.1113C>T
MANE Select: NM_005188
dbSNP: rs1949904161
Type: single nucleotide variant
Location: chr11:119278183 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 371: the 'required for ubiquitination of spred2' region; an α-helix; a modified residue (phosphotyrosine; by insr); a UniProt-annotated variant site (found in patients with acute myeloid leukemia; uncertain significance; loss of the ability to negatively regulate signaling pathways; promotes cell cycle progression; decreases apoptosis); the 'linker' 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.Tyr371Asn Pathogenic/Likely pathogenic ★★ same residue
CBL p.Tyr371Asp Pathogenic/Likely pathogenic ★★ same residue
CBL p.Tyr371Cys Pathogenic ★★ same residue
CBL p.Tyr371His Pathogenic/Likely pathogenic ★★ same residue
CBL p.Tyr371Ser Pathogenic/Likely pathogenic ★★ same residue
CBL p.Tyr371Phe Likely pathogenic ★ same residue
CBL p.Ala187Ser Uncertain significance ★★ ⚠ same condition
CBL p.Ala187Val 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-tyr371 (accessed [today's date]).

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