Is VCAN p.Val3294= (c.9882C>T) pathogenic?

VCAN p.Val3294= (c.9882C>T) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Val3294= (c.9882C>T)?

VCAN p.Val3294= (c.9882C>T) is associated with vitreoretinal degeneration, Wagner disease (ClinVar).

VCAN p.Val3294=

Q: How common is VCAN p.Val3294= (c.9882C>T) in the general population?

VCAN p.Val3294= (c.9882C>T) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9882C>T · rs308365 · VCV259379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

vitreoretinal degeneration

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.92 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.1	GERP 0.93, phastCons 1
Overall
CADD	9.623	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 100% East Asian · 44,865/44,868 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 96.7% 1,561,511/1,614,062 alleles · common exomes 1,413,159/1,461,740 · genomes 148,352/152,322 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
African / African-American	99.3%	1
South Asian	99.1%	1
Admixed American	98.4%	1
Ashkenazi Jewishnot grpmax-eligible	98.2%	1
Middle Eastern	97.4%	1
Remaining individualsnot grpmax-eligible	97.1%	1
European (non-Finnish)	96.2%	1
Finnishnot grpmax-eligible	95.8%	1
Amishnot grpmax-eligible	94.6%	1

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.Val3294=
Coding: c.9882C>T
MANE Select: NM_004385
dbSNP: rs308365
Type: single nucleotide variant
Location: chr5:83579981 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 3294: the sushi domain

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-val3294 (accessed [today's date]).

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