Is CUBN p.Pro1297Ser (c.3889C>T) pathogenic?

CUBN p.Pro1297Ser (c.3889C>T) is classified Uncertain significance in CUBN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-17). AlphaMissense: likely benign (0.3296); Absent from gnomAD v4.1; Associated with proteinuria, chronic benign.

What condition is associated with CUBN p.Pro1297Ser (c.3889C>T)?

CUBN p.Pro1297Ser (c.3889C>T) is associated with proteinuria, chronic benign (ClinVar).

How common is CUBN p.Pro1297Ser (c.3889C>T) in the general population?

CUBN p.Pro1297Ser (c.3889C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUBN p.Pro1297Ser (c.3889C>T)?

AlphaMissense predicts likely benign (score 0.3296) — an in-silico prediction, not a clinical call.

CUBN p.Pro1297Ser

c.3889C>T · rs2491931442 · VCV3254665

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3296 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

proteinuria, chronic benign

Computational evidence

Protein change
AlphaMissense	0.3296	likely benign
REVEL	0.547	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 55 kb · p 0.00014 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Pro1297Ser
Coding: c.3889C>T
MANE Select: NM_001081
dbSNP: rs2491931442
Type: single nucleotide variant
Location: chr10:17041161 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1297: a disulfide bond; the cub 8 domain; a UniProt-annotated variant site (in prochob); a UniProt-annotated variant site (in igs1; decreases strongly the cblif binding affinity); a turn

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

Similar variants

CUBN p.Pro1297Leu Pathogenic/Likely pathogenic ★★ ⚠ same residue
CUBN p.Pro1297= Likely benign ★ same residue
CUBN c.1230+1G>A Pathogenic/Likely pathogenic ★★ same condition
CUBN c.3672+2T>C 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-pro1297ser (accessed [today's date]).

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