Is VCAN p.Val1296= (c.3888G>A) pathogenic?

VCAN p.Val1296= (c.3888G>A) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). Ultra-rare (popmax 0.015%, amr).

How common is VCAN p.Val1296= (c.3888G>A) in the general population?

VCAN p.Val1296= (c.3888G>A) is ultra-rare (popmax 0.015%, amr) (gnomAD).

VCAN p.Val1296=

c.3888G>A · rs770238762 · VCV1574029

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.8	GERP -1.2, phastCons 0.99
Overall
CADD	2.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% Admixed American · 9/59,974 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.00218% 35/1,606,562 alleles · ultra-rare exomes 34/1,454,392 · genomes 1/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,664
European (non-Finnish)	0.00203%	49,163
Remaining individualsnot grpmax-eligible	0.0016%	62,428
African / African-American	0.00134%	74,884

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.Val1296=
Coding: c.3888G>A
MANE Select: NM_004385
dbSNP: rs770238762
Type: single nucleotide variant
Location: chr5:83522194 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1296: the 'disordered' region; 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-val1296 (accessed [today's date]).

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