Is VCAN p.Ser2473= (c.7419C>T) pathogenic?

VCAN p.Ser2473= (c.7419C>T) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.709%, nfe); Associated with Wagner disease.

What condition is associated with VCAN p.Ser2473= (c.7419C>T)?

VCAN p.Ser2473= (c.7419C>T) is associated with Wagner disease, vitreoretinal degeneration (ClinVar).

How common is VCAN p.Ser2473= (c.7419C>T) in the general population?

VCAN p.Ser2473= (c.7419C>T) is rare (popmax 0.709%, nfe) (gnomAD).

How is Wagner disease inherited?

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

VCAN p.Ser2473=

c.7419C>T · rs61754536 · VCV354440

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.709%, nfe)

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 -0.68	GERP -5.5
Overall
CADD	0.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.709% European (non-Finnish) · 8,363/1,179,950 alleles

Filtering AF 0.696% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.691%

Overall 0.735% 11,859/1,613,968 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.14%	32
Remaining individualsnot grpmax-eligible	0.733%	136
European (non-Finnish)grpmax	0.709%	141
Admixed American	0.607%	165
Ashkenazi Jewishnot grpmax-eligible	0.605%	165
South Asian	0.421%	238
Middle Eastern	0.281%	356
African / African-American	0.111%	904
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00446%	22,431

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser2473=
Coding: c.7419C>T
MANE Select: NM_004385
dbSNP: rs61754536
Type: single nucleotide variant
Location: chr5:83540422 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2473: the 'gag-beta' region; the 'disordered' 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 p.Ser2473Arg Uncertain significance ★ ⚠ same residue
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

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-ser2473 (accessed [today's date]).

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