Is CBL p.His360Tyr (c.1078C>T) pathogenic?

CBL p.His360Tyr (c.1078C>T) is classified Uncertain significance in CBL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-10). AlphaMissense: likely pathogenic (0.9852); Absent from gnomAD v4.1.

How common is CBL p.His360Tyr (c.1078C>T) in the general population?

CBL p.His360Tyr (c.1078C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBL p.His360Tyr (c.1078C>T)?

AlphaMissense predicts likely pathogenic (score 0.9852) — an in-silico prediction, not a clinical call.

CBL p.His360Tyr

c.1078C>T · rs933954615 · VCV1677649

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9852 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9852	likely pathogenic
REVEL	0.759	pathogenic-leaning
SaProt	LLR -13.11	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 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 22 kb · p 0.19 · regional, not allelic
Overall
CADD	27.8	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.His360Tyr
Coding: c.1078C>T
MANE Select: NM_005188
dbSNP: rs933954615
Type: single nucleotide variant
Location: chr11:119277827 (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

Similar variants

CBL p.His360Arg Uncertain significance ★ ⚠ same residue
CBL p.His360Asp Uncertain significance ★ ⚠ same residue
CBL p.His360Gln Uncertain significance ★ ⚠ same residue
CBL c.1096-1G>C Pathogenic/Likely pathogenic ★★ same type
CBL c.1096-1G>T Pathogenic ★★ same type
CBL c.1096-2A>T Pathogenic ★★ same type
CBL c.1228-2A>G Pathogenic/Likely pathogenic ★★ same type
CBL p.Arg420Gln Pathogenic/Likely pathogenic ★★ same type

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-his360tyr (accessed [today's date]).

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