Is CUBN p.Pro949Arg (c.2846C>G) pathogenic?

CUBN p.Pro949Arg (c.2846C>G) is classified Uncertain significance in CUBN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). AlphaMissense: likely benign (0.2104); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CUBN p.Pro949Arg (c.2846C>G)?

CUBN p.Pro949Arg (c.2846C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CUBN p.Pro949Arg (c.2846C>G) in the general population?

CUBN p.Pro949Arg (c.2846C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CUBN p.Pro949Arg (c.2846C>G)?

AlphaMissense predicts likely benign (score 0.2104) — an in-silico prediction, not a clinical call.

CUBN p.Pro949Arg

c.2846C>G · VCV3498581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2104 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2104	likely benign
REVEL	0.377	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 1.04	unconstrained · MANE · 84 kb · p 0.11 · 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.Pro949Arg
Coding: c.2846C>G
MANE Select: NM_001081
Type: single nucleotide variant
Location: chr10:17068226 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 949: a disulfide bond; the cub 5 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.Pro949Ser Uncertain significance ★★ same residue
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

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-pro949arg (accessed [today's date]).

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