Is CBL p.His39= (c.117C>T) pathogenic?

CBL p.His39= (c.117C>T) is classified Likely benign in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-13). No allele count reported in gnomAD v4.1 (AN 1,553,850); Associated with RASopathy.

What condition is associated with CBL p.His39= (c.117C>T)?

CBL p.His39= (c.117C>T) is associated with RASopathy (ClinVar).

How common is CBL p.His39= (c.117C>T) in the general population?

CBL p.His39= (c.117C>T) is no allele count reported in gnomAD v4.1 (AN 1,553,850) (gnomAD).

CBL p.His39=

c.117C>T · rs2496819504 · VCV2175645

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,553,850)

Conditions

RASopathy

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 2.7	GERP 0.013, phastCons 1
Overall
CADD	9.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,553,850). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBL
Protein: p.His39=
Coding: c.117C>T
MANE Select: NM_005188
dbSNP: rs2496819504
Type: single nucleotide variant
Location: chr11:119206534 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 39: the 'sufficient for interaction with ephb1' region

Full CBL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RASopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBL p.His39_His42dup Uncertain significance ★ same residue
CBL p.His39Pro Uncertain significance ★ ⚠ same residue
CBL p.His39Tyr Uncertain significance ★ ⚠ same residue
CBL c.1096-1G>C Pathogenic/Likely pathogenic ★★ same condition
CBL c.1096-1G>T Pathogenic ★★ same condition
CBL c.1228-2A>G Pathogenic/Likely pathogenic ★★ same condition
CBL p.Arg420Gln Pathogenic/Likely pathogenic ★★ same condition
CBL p.Arg420Leu Likely pathogenic ★★ 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-his39 (accessed [today's date]).

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