Is VCAN p.Ala285= (c.855G>T) pathogenic?

VCAN p.Ala285= (c.855G>T) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.065%, amr).

How common is VCAN p.Ala285= (c.855G>T) in the general population?

VCAN p.Ala285= (c.855G>T) is ultra-rare (popmax 0.065%, amr) (gnomAD).

VCAN p.Ala285=

c.855G>T · rs372962945 · VCV1103356

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.065%, 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 -8.1	GERP -4.9
Overall
CADD	0.322	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.065% Admixed American · 39/60,002 alleles

Filtering AF 0.0488% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0432%

Overall 0.0222% 359/1,614,042 alleles · ultra-rare exomes 323/1,461,890 · genomes 36/152,152 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.065%	1,539
European (non-Finnish)	0.0265%	3,770
Remaining individualsnot grpmax-eligible	0.008%	12,497
African / African-American	0.00267%	37,449

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.Ala285=
Coding: c.855G>T
MANE Select: NM_004385
dbSNP: rs372962945
Type: single nucleotide variant
Location: chr5:83512209 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 285: the link 2 domain

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

Similar variants

VCAN p.Ala285Glu Uncertain significance ★ same residue
VCAN p.Ala285Thr Uncertain significance ★ same residue
VCAN p.Ala285Val Conflicting classifications of pathogenicity ★ same residue
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

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-ala285 (accessed [today's date]).

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