Is VCAN p.Asp131= (c.393C>T) pathogenic?

VCAN p.Asp131= (c.393C>T) is classified Benign in VCAN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 9.14%, amr) — too common for a highly-penetrant pathogenic allele; Associated with vitreoretinal degeneration.

What condition is associated with VCAN p.Asp131= (c.393C>T)?

VCAN p.Asp131= (c.393C>T) is associated with vitreoretinal degeneration (ClinVar).

VCAN p.Asp131=

Q: How common is VCAN p.Asp131= (c.393C>T) in the general population?

VCAN p.Asp131= (c.393C>T) is common (popmax 9.14%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.393C>T · rs35042106 · VCV259364

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 9.14%, amr) — 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.1	GERP -4.5
Overall
CADD	0.573	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.14% Admixed American · 5,483/60,010 alleles

Filtering AF 8.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.85%

Overall 1.22% 19,616/1,614,104 alleles · common exomes 16,608/1,461,878 · genomes 3,008/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.14%	11
East Asian	7.17%	14
Finnishnot grpmax-eligible	3.08%	32
African / African-American	2.07%	48
Middle Eastern	1.81%	55
Remaining individualsnot grpmax-eligible	1.58%	63
Amishnot grpmax-eligible	1.43%	70
Ashkenazi Jewishnot grpmax-eligible	0.939%	107
European (non-Finnish)	0.476%	210
South Asian	0.42%	238

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.Asp131=
Coding: c.393C>T
MANE Select: NM_004385
dbSNP: rs35042106
Type: single nucleotide variant
Location: chr5:83490420 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 131: the ig-like v-type 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

Similar variants

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
VCAN p.His1946Tyr 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-asp131 (accessed [today's date]).

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