Is CBL p.His360Gln (c.1080T>A) pathogenic?

CBL p.His360Gln (c.1080T>A) is classified Uncertain significance in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). AlphaMissense: likely pathogenic (0.9929); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with CBL p.His360Gln (c.1080T>A)?

CBL p.His360Gln (c.1080T>A) is associated with Cardiovascular phenotype (ClinVar).

How common is CBL p.His360Gln (c.1080T>A) in the general population?

CBL p.His360Gln (c.1080T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBL p.His360Gln (c.1080T>A)?

AlphaMissense predicts likely pathogenic (score 0.9929) — an in-silico prediction, not a clinical call.

CBL p.His360Gln

c.1080T>A · VCV3485627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9929 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9929	likely pathogenic
REVEL	0.705	pathogenic-leaning
SaProt	LLR -12.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -1.5, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 22 kb · p 0.19 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CBL
Protein: p.His360Gln
Coding: c.1080T>A
MANE Select: NM_005188
Type: single nucleotide variant
Location: chr11:119277829 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 360: the 'required for ubiquitination of spred2' region; a β-strand; 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.His360Asp Uncertain significance ★ ⚠ same residue
CBL p.His360Tyr Uncertain significance ★★ ⚠ same residue
CBL p.His360Arg Uncertain significance ★ ⚠ same residue
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

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-his360gln (accessed [today's date]).

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