Is CUBN p.Gln84Ter (c.250C>T) pathogenic?

CUBN p.Gln84Ter (c.250C>T) is classified Likely pathogenic in CUBN (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD v4.1; Associated with Imerslund-Grasbeck syndrome.

What condition is associated with CUBN p.Gln84Ter (c.250C>T)?

CUBN p.Gln84Ter (c.250C>T) is associated with Imerslund-Grasbeck syndrome (ClinVar).

How common is CUBN p.Gln84Ter (c.250C>T) in the general population?

CUBN p.Gln84Ter (c.250C>T) 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.Gln84Ter

c.250C>T · rs386833774 · VCV56327

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 67
Splicing
SpliceAI	Δ0.54	donor gain · deltas
Pangolin	Δ0.52	gain · loss 0.51 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Overall
CADD	52.0	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

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: CUBN
Protein: p.Gln84Ter
Coding: c.250C>T
MANE Select: NM_001081
dbSNP: rs386833774
Type: single nucleotide variant
Location: chr10:17129123 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 84: an α-helix

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

Disease context

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

For Imerslund-Gräsbeck syndrome (Orphanet):

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

Similar variants

CUBN c.10033-1G>A Likely pathogenic ★★ same condition
CUBN c.1230+1G>A Pathogenic/Likely pathogenic ★★ same condition
CUBN c.3829+1G>A Pathogenic/Likely pathogenic ★★ same condition
CUBN c.4350+2T>C Likely pathogenic ★★ same condition
CUBN c.6822-1G>A Likely pathogenic ★★ same condition
CUBN c.8598+1G>T Likely pathogenic ★★ same condition
CUBN c.9454+1G>A Likely pathogenic ★★ same condition
CUBN p.Arg1487Ter Pathogenic/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/cubn-p-gln84ter (accessed [today's date]).

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