Is CUBN p.Ser2863Arg (c.8589C>G) pathogenic?

CUBN p.Ser2863Arg (c.8589C>G) is classified Uncertain significance in CUBN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely pathogenic (0.9298); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CUBN p.Ser2863Arg (c.8589C>G)?

CUBN p.Ser2863Arg (c.8589C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CUBN p.Ser2863Arg (c.8589C>G) in the general population?

CUBN p.Ser2863Arg (c.8589C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUBN p.Ser2863Arg (c.8589C>G)?

AlphaMissense predicts likely pathogenic (score 0.9298) — an in-silico prediction, not a clinical call.

CUBN p.Ser2863Arg

c.8589C>G · VCV4008284

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9298 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9298	likely pathogenic · top 5% in CUBN
REVEL	0.274	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.98, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 79 kb · p 0.98 · regional, not allelic
Overall
CADD	23.5	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.Ser2863Arg
Coding: c.8589C>G
MANE Select: NM_001081
Type: single nucleotide variant
Location: chr10:16899005 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2863: a disulfide bond; a UniProt-annotated variant site (in prochob); the cub 21 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CUBN p.Arg2444Ter Pathogenic ★★ same condition
CUBN p.Ala1501Glu Uncertain significance ★★ same condition
CUBN p.Ala2086Thr Uncertain significance ★★ same condition
CUBN p.Ala238Val Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1268Cys Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1345Trp Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1636Trp Uncertain significance ★★ ⚠ same condition
CUBN p.Arg1695His Uncertain significance ★★ 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-ser2863arg (accessed [today's date]).

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