Is VCAN p.Val477= (c.1431C>T) pathogenic?

VCAN p.Val477= (c.1431C>T) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-28). Ultra-rare (popmax 0.0387%, afr).

How common is VCAN p.Val477= (c.1431C>T) in the general population?

VCAN p.Val477= (c.1431C>T) is ultra-rare (popmax 0.0387%, afr) (gnomAD).

VCAN p.Val477=

c.1431C>T · rs369643543 · VCV1115260

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0387%, afr)

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 -0.32	GERP -1.3
Overall
CADD	1.243	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0387% African / African-American · 29/74,914 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.00397% 64/1,613,970 alleles · ultra-rare exomes 48/1,461,834 · genomes 16/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0387%	2,583
Remaining individualsnot grpmax-eligible	0.0096%	10,414
European (non-Finnish)	0.0022%	45,384
South Asian	0.0022%	45,536
Admixed American	0.00167%	59,998

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.Val477=
Coding: c.1431C>T
MANE Select: NM_004385
dbSNP: rs369643543
Type: single nucleotide variant
Location: chr5:83519737 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 477: the 'gag-alpha (glucosaminoglycan attachment domain)' region

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-val477 (accessed [today's date]).

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