Is VCAN p.Ala20= (c.60G>A) pathogenic?

VCAN p.Ala20= (c.60G>A) is classified Likely benign in VCAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). Very rare (popmax 0.00549%, sas).

How common is VCAN p.Ala20= (c.60G>A) in the general population?

VCAN p.Ala20= (c.60G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

VCAN p.Ala20=

c.60G>A · rs755828566 · VCV1607334

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

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 -1.6	GERP -4.3
Overall
CADD	1.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,054 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000744% 12/1,613,040 alleles · very rare exomes 10/1,460,938 · genomes 2/152,102 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,211
East Asian	0.00447%	22,385
Remaining individualsnot grpmax-eligible	0.0032%	31,225
European (non-Finnish)	0.000254%	393,128

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.Ala20=
Coding: c.60G>A
MANE Select: NM_004385
dbSNP: rs755828566
Type: single nucleotide variant
Location: chr5:83483578 (GRCh38)
Gene constraint: LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)

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

Similar variants

VCAN p.Ala20Val 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-ala20 (accessed [today's date]).

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