Is CUBN p.Pro3428= (c.10284C>G) pathogenic?

CUBN p.Pro3428= (c.10284C>G) is classified Likely benign in CUBN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). Absent from gnomAD v4.1.

How common is CUBN p.Pro3428= (c.10284C>G) in the general population?

CUBN p.Pro3428= (c.10284C>G) is absent from gnomAD v4.1 (gnomAD).

CUBN p.Pro3428=

c.10284C>G · VCV4906634

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -9	GERP -3.4
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CUBN
Protein: p.Pro3428=
Coding: c.10284C>G
MANE Select: NM_001081
Type: single nucleotide variant
Location: chr10:16835092 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3428: a UniProt-annotated variant site (in prochob); the cub 26 domain

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

Similar variants

CUBN p.Pro3428Leu Uncertain significance ★★ same residue
CUBN p.Pro3428Ser Uncertain significance ★★ same residue
CUBN c.10033-1G>A Likely pathogenic ★★ same type
CUBN c.1230+1G>A Pathogenic/Likely pathogenic ★★ same type
CUBN c.3672+2T>C Likely pathogenic ★★ same type
CUBN c.3829+1G>A Pathogenic/Likely pathogenic ★★ same type
CUBN c.4350+2T>C Likely pathogenic ★★ same type
CUBN c.6821+3A>G Pathogenic/Likely pathogenic ★★ same type

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-pro3428 (accessed [today's date]).

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