Is VCAN p.Ile210= (c.630C>T) pathogenic?

VCAN p.Ile210= (c.630C>T) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-10). Rare (popmax 0.273%, sas); Associated with Wagner disease.

What condition is associated with VCAN p.Ile210= (c.630C>T)?

VCAN p.Ile210= (c.630C>T) is associated with Wagner disease, vitreoretinal degeneration (ClinVar).

How common is VCAN p.Ile210= (c.630C>T) in the general population?

VCAN p.Ile210= (c.630C>T) is rare (popmax 0.273%, sas) (gnomAD).

How is Wagner disease inherited?

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

VCAN p.Ile210=

c.630C>T · rs538498172 · VCV903717

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.273%, sas)

Conditions

Wagner disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.35	GERP -1.1, phastCons 0.98
Overall
CADD	8.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.273% South Asian · 249/91,078 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.235%

Overall 0.0166% 268/1,614,124 alleles · rare exomes 252/1,461,860 · genomes 16/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.273%	366
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,012
African / African-American	0.00133%	75,020
European (non-Finnish)	8.47e-05%	1,180,012

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.Ile210=
Coding: c.630C>T
MANE Select: NM_004385
dbSNP: rs538498172
Type: single nucleotide variant
Location: chr5:83493813 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 210: the link 1 domain

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-ile210 (accessed [today's date]).

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