Is CUBN p.Pro2013= (c.6039C>T) pathogenic?

CUBN p.Pro2013= (c.6039C>T) is classified Benign/Likely benign in CUBN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-19). Ultra-rare (popmax 0.0178%, eas); Associated with proteinuria, chronic benign.

What condition is associated with CUBN p.Pro2013= (c.6039C>T)?

CUBN p.Pro2013= (c.6039C>T) is associated with proteinuria, chronic benign, Imerslund-Grasbeck syndrome, Imerslund-Grasbeck syndrome type 1 (ClinVar).

How common is CUBN p.Pro2013= (c.6039C>T) in the general population?

CUBN p.Pro2013= (c.6039C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

CUBN p.Pro2013=

c.6039C>T · rs149569558 · VCV699668

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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 -4.5	GERP -3.4
Overall
CADD	0.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,878 alleles

Filtering AF 0.0138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.0231% 373/1,614,050 alleles · ultra-rare exomes 347/1,461,848 · genomes 26/152,202 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.228%	438
Remaining individualsnot grpmax-eligible	0.0208%	4,808
East Asiangrpmax	0.0178%	5,610
Middle Eastern	0.0165%	6,060
South Asian	0.0165%	6,071
European (non-Finnish)	0.0157%	6,378
African / African-American	0.004%	25,007
Admixed American	0.00333%	29,999

Finnish 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.Pro2013=
Coding: c.6039C>T
MANE Select: NM_001081
dbSNP: rs149569558
Type: single nucleotide variant
Location: chr10:16933172 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2013: 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-pro2013 (accessed [today's date]).

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