Is CUBN p.Pro271= (c.813C>T) pathogenic?

CUBN p.Pro271= (c.813C>T) is classified Likely benign in CUBN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0601%, amr); Associated with proteinuria, chronic benign.

What condition is associated with CUBN p.Pro271= (c.813C>T)?

CUBN p.Pro271= (c.813C>T) is associated with proteinuria, chronic benign, Imerslund-Grasbeck syndrome, Imerslund-Grasbeck syndrome type 1 (ClinVar).

How common is CUBN p.Pro271= (c.813C>T) in the general population?

CUBN p.Pro271= (c.813C>T) is ultra-rare (popmax 0.0601%, amr) (gnomAD).

CUBN p.Pro271=

c.813C>T · rs139348777 · VCV698776

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0601%, amr)

Conditions

proteinuria, chronic benign

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 -6.5	GERP -3.8
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0601% Admixed American · 36/59,928 alleles

Filtering AF 0.0445% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.00663% 107/1,613,316 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0601%	1,665
African / African-American	0.0506%	1,974
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.0144%	6,942
East Asian	0.00446%	22,419
South Asian	0.0022%	45,389
European (non-Finnish)	0.00161%	62,090

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.Pro271=
Coding: c.813C>T
MANE Select: NM_001081
dbSNP: rs139348777
Type: single nucleotide variant
Location: chr10:17114097 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 271: a disulfide bond; the egf-like 3; calcium-binding domain

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

Disease context

proteinuria, chronic benign — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Imerslund-Grasbeck syndrome Imerslund-Grasbeck syndrome type 1

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-pro271 (accessed [today's date]).

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