Is VCAN p.Pro1088= (c.3264A>G) pathogenic?

VCAN p.Pro1088= (c.3264A>G) is classified Uncertain significance in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 8.47e-05%, nfe); Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Pro1088= (c.3264A>G)?

VCAN p.Pro1088= (c.3264A>G) is associated with vitreoretinal degeneration (ClinVar).

How common is VCAN p.Pro1088= (c.3264A>G) in the general population?

VCAN p.Pro1088= (c.3264A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

VCAN p.Pro1088=

c.3264A>G · rs767745674 · VCV354417

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

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 -0.22	GERP -4.7
Overall
CADD	1.624	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,024 alleles

Overall 6.2e-05% 1/1,614,114 alleles · very rare exomes 1/1,461,764 · genomes 0/152,350 · joint denominator

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.Pro1088=
Coding: c.3264A>G
MANE Select: NM_004385
dbSNP: rs767745674
Type: single nucleotide variant
Location: chr5:83521570 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1088: the 'gag-alpha (glucosaminoglycan attachment domain)' 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

Similar variants

VCAN p.Pro1088Ser Uncertain significance ★ ⚠ same residue
VCAN c.*905A>G Uncertain significance ★★ same condition
VCAN p.Ala2446Val Uncertain significance ★★ ⚠ same condition
VCAN p.Arg1431His Uncertain significance ★★ ⚠ same condition
VCAN p.Glu2277Lys Uncertain significance ★★ ⚠ same condition
VCAN p.Gly1068Ser Uncertain significance ★★ ⚠ same condition
VCAN p.Gly2758Cys Uncertain significance ★★ ⚠ same condition
VCAN p.Gly914Asp 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-pro1088 (accessed [today's date]).

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