Is CBL p.His40Asp (c.118C>G) pathogenic?

CBL p.His40Asp (c.118C>G) is classified Uncertain significance in CBL (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-01). AlphaMissense: ambiguous (0.4028); Absent from gnomAD v4.1.

How common is CBL p.His40Asp (c.118C>G) in the general population?

CBL p.His40Asp (c.118C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBL p.His40Asp (c.118C>G)?

AlphaMissense predicts ambiguous (score 0.4028) — an in-silico prediction, not a clinical call.

CBL p.His40Asp

c.118C>G · rs1949270382 · VCV928600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4028 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4028	ambiguous
REVEL	0.343	indeterminate
SaProt	LLR -12.20	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 26 kb · p 0.76 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

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.His40Asp
Coding: c.118C>G
MANE Select: NM_005188
dbSNP: rs1949270382
Type: single nucleotide variant
Location: chr11:119206535 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 64.27 · 34 PDB
Residue 40: the 'sufficient for interaction with ephb1' region

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

Similar variants

CBL p.His40= Likely benign ★★ same residue
CBL p.His40Gln Uncertain significance ★ ⚠ same residue
CBL p.His40Leu Uncertain significance ★ ⚠ same residue
CBL p.His40_His42del 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

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-his40asp (accessed [today's date]).

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