Is CUBN p.Pro672= (c.2016G>A) pathogenic?

CUBN p.Pro672= (c.2016G>A) is classified Benign/Likely benign in CUBN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-12). Rare (popmax 0.363%, eas); Associated with Imerslund-Grasbeck syndrome type 1.

What condition is associated with CUBN p.Pro672= (c.2016G>A)?

CUBN p.Pro672= (c.2016G>A) is associated with Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome, proteinuria, chronic benign (ClinVar).

How common is CUBN p.Pro672= (c.2016G>A) in the general population?

CUBN p.Pro672= (c.2016G>A) is rare (popmax 0.363%, eas) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

CUBN p.Pro672=

c.2016G>A · rs148107237 · VCV299516

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.363%, eas)

Conditions

Imerslund-Grasbeck syndrome type 1

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 -5	GERP -3.7
Overall
CADD	1.082	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% East Asian · 163/44,864 alleles

Filtering AF 0.318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.3%

Overall 0.0171% 276/1,613,808 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.363%	275
South Asian	0.0571%	1,751
Remaining individualsnot grpmax-eligible	0.032%	3,125
Admixed American	0.00333%	29,998
European (non-Finnish)	0.00322%	31,048
African / African-American	0.00133%	75,004

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.Pro672=
Coding: c.2016G>A
MANE Select: NM_001081
dbSNP: rs148107237
Type: single nucleotide variant
Location: chr10:17085691 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 672: the cub 2 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: Imerslund-Grasbeck syndrome proteinuria, chronic benign

For Imerslund-Gräsbeck syndrome (Orphanet):

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

Similar variants

CUBN p.Pro672Leu Uncertain significance ★★ same residue
CUBN p.Pro672Arg Uncertain significance ★ same residue
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

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-pro672 (accessed [today's date]).

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