Is VCAN p.Asp2480Val (c.7439A>T) pathogenic?

VCAN p.Asp2480Val (c.7439A>T) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-03). AlphaMissense: likely benign (0.144); Rare (popmax 0.111%, sas).

How common is VCAN p.Asp2480Val (c.7439A>T) in the general population?

VCAN p.Asp2480Val (c.7439A>T) is rare (popmax 0.111%, sas) (gnomAD).

What do computational predictors say about VCAN p.Asp2480Val (c.7439A>T)?

AlphaMissense predicts likely benign (score 0.144) — an in-silico prediction, not a clinical call.

VCAN p.Asp2480Val

c.7439A>T · rs538228734 · VCV1529957

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.144 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.111%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.144	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP 0.059, phastCons 0.004
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	18.13	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% South Asian · 101/91,080 alleles

Filtering AF 0.0933% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0868%

Overall 0.00669% 108/1,614,016 alleles · rare exomes 102/1,461,766 · genomes 6/152,250 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.111%	902
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.000254%	393,315

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.Asp2480Val
Coding: c.7439A>T
MANE Select: NM_004385
dbSNP: rs538228734
Type: single nucleotide variant
Location: chr5:83540442 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 2480: the 'gag-beta' region

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

Similar variants

VCAN p.Asp2480Asn Uncertain significance ★ ⚠ 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
VCAN c.9266-5G>A Uncertain significance ★★ same type
VCAN c.9493+5G>A 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-asp2480val (accessed [today's date]).

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