Is VCAN p.Pro2878= (c.8634A>G) pathogenic?

VCAN p.Pro2878= (c.8634A>G) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-13). Ultra-rare (popmax 0.0583%, amr); Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Pro2878= (c.8634A>G)?

VCAN p.Pro2878= (c.8634A>G) is associated with vitreoretinal degeneration, Wagner disease (ClinVar).

How common is VCAN p.Pro2878= (c.8634A>G) in the general population?

VCAN p.Pro2878= (c.8634A>G) is ultra-rare (popmax 0.0583%, amr) (gnomAD).

VCAN p.Pro2878=

c.8634A>G · rs200031614 · VCV906620

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0583%, amr)

Conditions

vitreoretinal degeneration

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 1.5	GERP -1.9
Overall
CADD	11.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0583% Admixed American · 35/59,998 alleles

Filtering AF 0.0431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0378%

Overall 0.0108% 174/1,613,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0583%	1,714
European (non-Finnish)	0.0111%	9,008
Remaining individualsnot grpmax-eligible	0.0064%	15,627
African / African-American	0.00533%	18,755

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: VCAN
Protein: p.Pro2878=
Coding: c.8634A>G
MANE Select: NM_004385
dbSNP: rs200031614
Type: single nucleotide variant
Location: chr5:83541637 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2878: the 'gag-beta' region

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

Disease context

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

Also linked: Wagner disease

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-pro2878 (accessed [today's date]).

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