Is VCAN p.Val1587= (c.4761T>A) pathogenic?

VCAN p.Val1587= (c.4761T>A) is classified Uncertain significance in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Absent from gnomAD v4.1; Associated with Wagner disease.

What condition is associated with VCAN p.Val1587= (c.4761T>A)?

VCAN p.Val1587= (c.4761T>A) is associated with Wagner disease, vitreoretinal degeneration (ClinVar).

How common is VCAN p.Val1587= (c.4761T>A) in the general population?

VCAN p.Val1587= (c.4761T>A) is absent from gnomAD v4.1 (gnomAD).

How is Wagner disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

VCAN p.Val1587=

c.4761T>A · rs1746783267 · VCV904001

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Wagner disease

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 -0.39	GERP -5.4
Overall
CADD	0.811	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: VCAN
Protein: p.Val1587=
Coding: c.4761T>A
MANE Select: NM_004385
dbSNP: rs1746783267
Type: single nucleotide variant
Location: chr5:83537764 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1587: the 'gag-beta' region

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

Disease context

Wagner disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: vitreoretinal degeneration

For Wagner disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

VCAN c.4004-1G>A Pathogenic ★★ same condition
VCAN c.4004-2A>C Pathogenic ★★ same condition
VCAN c.4004-2A>G Pathogenic ★★ same condition
VCAN c.4004-5T>C Pathogenic ★★ same condition
VCAN c.9265+1G>C Pathogenic ★★ same condition
VCAN c.9266-5G>A Uncertain significance ★★ same condition
VCAN c.*905A>G Uncertain significance ★★ same condition
VCAN p.Ala2446Val 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/vcan-p-val1587 (accessed [today's date]).

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