Is CBLB p.Arg468Ter (c.1402C>T) pathogenic?

CBLB p.Arg468Ter (c.1402C>T) is classified Pathogenic in CBLB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-06-28). Very rare (popmax 0.00134%, afr); Associated with autoimmune disease, multisystem, infantile-onset, 3.

What condition is associated with CBLB p.Arg468Ter (c.1402C>T)?

CBLB p.Arg468Ter (c.1402C>T) is associated with autoimmune disease, multisystem, infantile-onset, 3 (ClinVar).

How common is CBLB p.Arg468Ter (c.1402C>T) in the general population?

CBLB p.Arg468Ter (c.1402C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

CBLB p.Arg468Ter

c.1402C>T · rs535219619 · VCV2506977

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

autoimmune disease, multisystem, infantile-onset, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 19
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1.4, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,872 alleles

Overall 0.000658% 1/152,042 alleles · very rare

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: CBLB
Protein: p.Arg468Ter
Coding: c.1402C>T
MANE Select: NM_170662
dbSNP: rs535219619
Type: single nucleotide variant
Location: chr3:105720052 (GRCh38)
Gene constraint: LOEUF 0.406 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.88 · 36 PDB
Residue 468: a UniProt-annotated variant site (in admio3; likely pathogenic); the 'disordered' region

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

Disease context

autoimmune disease, multisystem, infantile-onset, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CBLB c.2569+1609A>C Uncertain significance ★ same condition
CBLB p.Cys436Trp Pathogenic same condition
CBLB p.His257Leu Pathogenic same condition
CBLB c.2689+2del Likely pathogenic ★ same condition
CBLB p.Arg670Gln Benign/Likely benign ★★ same type
CBLB p.Pro387= Benign ★★ same type
CBLB p.Pro689= Benign/Likely benign ★★ same type
CBLB p.Ser622Thr Benign/Likely benign ★★ 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/cblb-p-arg468ter (accessed [today's date]).

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