Is VCAN p.Asp994= (c.2982T>C) pathogenic?

VCAN p.Asp994= (c.2982T>C) is classified Likely benign in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). Very rare (popmax 0.00133%, afr).

How common is VCAN p.Asp994= (c.2982T>C) in the general population?

VCAN p.Asp994= (c.2982T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

VCAN p.Asp994=

c.2982T>C · VCV3613343

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, 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 -0.26	GERP -5, phastCons 0.002
Overall
CADD	4.566	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,938 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,984 alleles · very rare exomes 3/1,461,754 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,938
European (non-Finnish)	0.000254%	393,314

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.Asp994=
Coding: c.2982T>C
MANE Select: NM_004385
Type: single nucleotide variant
Location: chr5:83521288 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 994: 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-asp994 (accessed [today's date]).

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