VCAN p.Val2986=
c.8958C>T · rs1402366948 · VCV2985259
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00246%, 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 -5.1 | GERP -5.7 |
| Overall | ||
| CADD | 0.344 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00246%
European (non-Finnish) · 29/1,179,958 alleles
Filtering AF
0.00172%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00149%
Overall
0.00204%
33/1,613,836 alleles · very rare
exomes 31/1,461,712 · genomes 2/152,124 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00246% | 40,688 |
| East Asian | 0.00223% | 44,850 |
| Admixed American | 0.00167% | 59,974 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,478 |
| South Asian | 0.0011% | 91,062 |
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.Val2986=
- Coding
- c.8958C>T
- MANE Select
- NM_004385
- dbSNP
- rs1402366948
- Type
- single nucleotide variant
- Location
- chr5:83541961 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 2986
- the 'gag-beta' region
Similar variants
- VCAN p.Val2986Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
- VCAN p.Val2986Phe 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
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-val2986 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown