Is CUBN p.Ser1947= (c.5841C>T) pathogenic?

CUBN p.Ser1947= (c.5841C>T) is classified Likely benign in CUBN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). Ultra-rare (popmax 0.0512%, eas); Associated with Imerslund-Grasbeck syndrome type 1.

What condition is associated with CUBN p.Ser1947= (c.5841C>T)?

CUBN p.Ser1947= (c.5841C>T) is associated with Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome, proteinuria, chronic benign (ClinVar).

How common is CUBN p.Ser1947= (c.5841C>T) in the general population?

CUBN p.Ser1947= (c.5841C>T) is ultra-rare (popmax 0.0512%, eas) (gnomAD).

How is Imerslund-Gräsbeck syndrome inherited?

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

CUBN p.Ser1947=

c.5841C>T · rs199868206 · VCV696243

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0512%, 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 -3.4	GERP -2.7
Overall
CADD	1.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0512% East Asian · 23/44,880 alleles

Filtering AF 0.035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0296%

Overall 0.00607% 98/1,613,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0512%	1,951
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0144%	6,942
South Asian	0.00769%	13,009
European (non-Finnish)	0.00466%	21,454
Admixed American	0.00167%	59,970
African / African-American	0.00134%	74,896

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.Ser1947=
Coding: c.5841C>T
MANE Select: NM_001081
dbSNP: rs199868206
Type: single nucleotide variant
Location: chr10:16937677 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1947: a UniProt-annotated variant site (in prochob); a UniProt-annotated variant site (in prochob; uncertain significance); the cub 13 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.Ser1947Phe Uncertain significance ★ same residue
CUBN p.Ser1947Tyr Conflicting classifications of pathogenicity ★ 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-ser1947 (accessed [today's date]).

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