Is CUBN p.Val815= (c.2445C>T) pathogenic?

CUBN p.Val815= (c.2445C>T) is classified Benign/Likely benign in CUBN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.89%, afr); Associated with Imerslund-Grasbeck syndrome.

What condition is associated with CUBN p.Val815= (c.2445C>T)?

CUBN p.Val815= (c.2445C>T) is associated with Imerslund-Grasbeck syndrome, Imerslund-Grasbeck syndrome type 1 (ClinVar).

How common is CUBN p.Val815= (c.2445C>T) in the general population?

CUBN p.Val815= (c.2445C>T) is low-frequency (popmax 1.89%, afr) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

CUBN p.Val815=

c.2445C>T · rs116350428 · VCV299509

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.89%, afr)

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.84 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -3.1
Overall
CADD	0.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.89% African / African-American · 1,416/74,910 alleles

Filtering AF 1.81% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.78%

Overall 0.101% 1,627/1,611,580 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.89%	53
Admixed American	0.135%	740
Remaining individualsnot grpmax-eligible	0.128%	779
Middle Eastern	0.0587%	1,703
South Asian	0.0364%	2,746
East Asian	0.00446%	22,415
European (non-Finnish)	0.00102%	98,282

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: CUBN
Protein: p.Val815=
Coding: c.2445C>T
MANE Select: NM_001081
dbSNP: rs116350428
Type: single nucleotide variant
Location: chr10:17071828 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 815: the cub 3 domain

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

Also linked: Imerslund-Grasbeck syndrome type 1

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.3672+2T>C 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.6821+3A>G Pathogenic/Likely pathogenic ★★ same condition
CUBN c.6822-1G>A Likely pathogenic ★★ same condition
CUBN c.8598+1G>T 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-val815 (accessed [today's date]).

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