Is CUBN p.Pro1988= (c.5964C>T) pathogenic?

CUBN p.Pro1988= (c.5964C>T) is classified Likely benign in CUBN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-15). Ultra-rare (popmax 0.0133%, afr); Associated with proteinuria, chronic benign.

What condition is associated with CUBN p.Pro1988= (c.5964C>T)?

CUBN p.Pro1988= (c.5964C>T) is associated with proteinuria, chronic benign, Imerslund-Grasbeck syndrome, Imerslund-Grasbeck syndrome type 1 (ClinVar).

How common is CUBN p.Pro1988= (c.5964C>T) in the general population?

CUBN p.Pro1988= (c.5964C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

CUBN p.Pro1988=

c.5964C>T · rs539618523 · VCV1670809

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

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 -11	GERP -3.1
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,996 alleles

Filtering AF 0.00722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00595% 96/1,613,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,500
South Asian	0.00988%	10,119
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)	0.00602%	16,619
Admixed American	0.00167%	60,006

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.Pro1988=
Coding: c.5964C>T
MANE Select: NM_001081
dbSNP: rs539618523
Type: single nucleotide variant
Location: chr10:16933247 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1988: a disulfide bond; a UniProt-annotated variant site (in prochob); the cub 14 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-pro1988 (accessed [today's date]).

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