Is CUBN p.Asn313= (c.939C>T) pathogenic?

CUBN p.Asn313= (c.939C>T) is classified Benign in CUBN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 29%, mid) — too common for a highly-penetrant pathogenic allele; Associated with Imerslund-Grasbeck syndrome.

What condition is associated with CUBN p.Asn313= (c.939C>T)?

CUBN p.Asn313= (c.939C>T) is associated with Imerslund-Grasbeck syndrome, Imerslund-Grasbeck syndrome type 1 (ClinVar).

How is Imerslund-Gräsbeck syndrome inherited?

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

CUBN p.Asn313=

Q: How common is CUBN p.Asn313= (c.939C>T) in the general population?

CUBN p.Asn313= (c.939C>T) is common (popmax 29%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.939C>T · rs1801223 · VCV299533

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 29%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

Imerslund-Grasbeck syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.64	GERP -3.2
Overall
CADD	1.325	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29% Middle Eastern · 1,756/6,060 alleles

Filtering AF 27.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.4%

Overall 19.6% 315,475/1,613,428 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	30.2%	3
Middle Easterngrpmax	29%	3
Finnishnot grpmax-eligible	26.4%	4
East Asian	25.7%	4
Admixed American	21.8%	5
African / African-American	21.6%	5
Remaining individualsnot grpmax-eligible	20.5%	5
European (non-Finnish)	18.5%	5
South Asian	17.3%	6
Amishnot grpmax-eligible	16.3%	6

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn313=
Coding: c.939C>T
MANE Select: NM_001081
dbSNP: rs1801223
Type: single nucleotide variant
Location: chr10:17110995 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 313: the egf-like 4; calcium-binding 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-asn313 (accessed [today's date]).

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