Is VCAN p.Cys294= (c.882C>T) pathogenic?

VCAN p.Cys294= (c.882C>T) is classified Likely benign in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). Very rare (popmax 0.005%, amr).

How common is VCAN p.Cys294= (c.882C>T) in the general population?

VCAN p.Cys294= (c.882C>T) is very rare (popmax 0.005%, amr) (gnomAD).

VCAN p.Cys294=

c.882C>T · rs751444743 · VCV1576876

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -4.6	GERP -4.9
Overall
CADD	8.634	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,992 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00192% 31/1,613,978 alleles · very rare exomes 27/1,461,884 · genomes 4/152,094 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,997
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00195%	51,306
Finnishnot grpmax-eligible	0.00156%	64,024
African / African-American	0.00134%	74,886

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.Cys294=
Coding: c.882C>T
MANE Select: NM_004385
dbSNP: rs751444743
Type: single nucleotide variant
Location: chr5:83512236 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 294: the link 2 domain; a disulfide bond

Full VCAN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VCAN c.4004-1G>A Pathogenic ★★ same type
VCAN c.4004-2A>C Pathogenic ★★ same type
VCAN c.4004-2A>G Pathogenic ★★ same type
VCAN c.4004-5T>C Pathogenic ★★ same type
VCAN c.9265+1G>C Pathogenic ★★ same type
VCAN c.9266-5G>A Uncertain significance ★★ same type
VCAN c.9493+5G>A Uncertain significance ★★ same type
VCAN c.9493+5G>T Uncertain significance ★★ same type

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-cys294 (accessed [today's date]).

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