Is CUBN p.Pro833fs (c.2496del) pathogenic?

CUBN p.Pro833fs (c.2496del) is classified Likely pathogenic in CUBN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). Absent from gnomAD v4.1; Associated with Imerslund-Grasbeck syndrome type 1.

What condition is associated with CUBN p.Pro833fs (c.2496del)?

CUBN p.Pro833fs (c.2496del) is associated with Imerslund-Grasbeck syndrome type 1, proteinuria, chronic benign (ClinVar).

How common is CUBN p.Pro833fs (c.2496del) in the general population?

CUBN p.Pro833fs (c.2496del) is absent from gnomAD v4.1 (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CUBN p.Pro833fs

c.2496del · VCV3593672

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,802)

Conditions

Imerslund-Grasbeck syndrome type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 19 of 67
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,802). 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: CUBN
Protein: p.Pro833fs
Coding: c.2496del
MANE Select: NM_001081
Type: Deletion
Location: chr10:17071555 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 833: the cub 4 domain

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

Disease context

Imerslund-Grasbeck syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: proteinuria, chronic benign

For Imerslund-Gräsbeck syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Finland)

Similar variants

CUBN c.7001-2del Likely pathogenic ★★ same condition
CUBN p.Ala1031_Tyr1032insTer Pathogenic/Likely pathogenic ★★ same condition
CUBN p.Ala2708_Tyr2709insTer Pathogenic/Likely pathogenic ★★ same condition
CUBN p.Arg1487fs Pathogenic/Likely pathogenic ★★ same condition
CUBN p.Asn1658fs Pathogenic/Likely pathogenic ★★ same condition
CUBN p.Glu2310fs Pathogenic/Likely pathogenic ★★ same condition
CUBN p.Phe3204fs Likely pathogenic ★★ same condition
CUBN p.Thr622fs 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/cubn-p-pro833fs (accessed [today's date]).

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