Is VCAN p.Asp1237Asn (c.3709G>A) pathogenic?

VCAN p.Asp1237Asn (c.3709G>A) is classified Likely benign in VCAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-15). AlphaMissense: likely benign (0.1363); Ultra-rare (popmax 0.0847%, eas).

How common is VCAN p.Asp1237Asn (c.3709G>A) in the general population?

VCAN p.Asp1237Asn (c.3709G>A) is ultra-rare (popmax 0.0847%, eas) (gnomAD).

What do computational predictors say about VCAN p.Asp1237Asn (c.3709G>A)?

AlphaMissense predicts likely benign (score 0.1363) — an in-silico prediction, not a clinical call.

VCAN p.Asp1237Asn

c.3709G>A · rs144202228 · VCV1084921

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1363 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0847%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1363	likely benign
REVEL	0.265	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 26 kb · p 0.23 · regional, not allelic
Overall
CADD	20.2	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 0.0847% East Asian · 38/44,878 alleles

Filtering AF 0.0634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.056%

Overall 0.00273% 44/1,614,100 alleles · ultra-rare exomes 30/1,461,858 · genomes 14/152,242 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0847%	1,181
Remaining individualsnot grpmax-eligible	0.0048%	20,835
Admixed American	0.00167%	60,006
European (non-Finnish)	0.000169%	590,009

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.Asp1237Asn
Coding: c.3709G>A
MANE Select: NM_004385
dbSNP: rs144202228
Type: single nucleotide variant
Location: chr5:83522015 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 1237: 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-asp1237asn (accessed [today's date]).

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