Is VCAN p.Ser3006= (c.9018T>A) pathogenic?

VCAN p.Ser3006= (c.9018T>A) is classified Benign/Likely benign in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-29). Rare (popmax 0.488%, afr).

How common is VCAN p.Ser3006= (c.9018T>A) in the general population?

VCAN p.Ser3006= (c.9018T>A) is rare (popmax 0.488%, afr) (gnomAD).

VCAN p.Ser3006=

c.9018T>A · rs142894260 · VCV768016

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.488%, afr)

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 0.16	GERP -1, phastCons 0.004
Overall
CADD	3.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.488% African / African-American · 365/74,846 alleles

Filtering AF 0.446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.43%

Overall 0.0268% 431/1,610,202 alleles · rare exomes 205/1,457,900 · genomes 226/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.488%	205
Admixed American	0.0536%	1,867
Remaining individualsnot grpmax-eligible	0.0433%	2,307
Middle Eastern	0.0166%	6,038
European (non-Finnish)	0.00051%	196,211

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.Ser3006=
Coding: c.9018T>A
MANE Select: NM_004385
dbSNP: rs142894260
Type: single nucleotide variant
Location: chr5:83542021 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Residue 3006: the 'gag-beta' 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-ser3006 (accessed [today's date]).

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