VCAN p.Asp246=
c.738T>C · rs1011389266 · VCV2717115
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, nfe)
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 -0.18 | GERP -1.4, phastCons 0.01 |
| Overall | ||
| CADD | 9.262 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
European (non-Finnish) · 13/1,179,982 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.000867%
14/1,614,114 alleles · very rare
exomes 14/1,461,808 · genomes 0/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0011% | 90,768 |
| South Asian | 0.0011% | 91,066 |
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.Asp246=
- Coding
- c.738T>C
- MANE Select
- NM_004385
- dbSNP
- rs1011389266
- Type
- single nucleotide variant
- Location
- chr5:83493921 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
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-asp246 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown