VCAN p.Asp174=
c.522C>T · rs150142826 · VCV1157485
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0286%, nfe)
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 -4.3 | GERP -4.8 |
| Overall | ||
| CADD | 6.972 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0286%
European (non-Finnish) · 337/1,180,024 alleles
Filtering AF
0.026%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.025%
Overall
0.0224%
362/1,613,896 alleles · ultra-rare
exomes 340/1,461,832 · genomes 22/152,064 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0286% | 3,502 |
| Remaining individualsnot grpmax-eligible | 0.0192% | 5,206 |
| Admixed American | 0.00833% | 12,000 |
| East Asian | 0.00446% | 22,443 |
| South Asian | 0.00329% | 30,359 |
| African / African-American | 0.00267% | 37,426 |
| Finnishnot grpmax-eligible | 0.00156% | 64,006 |
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.Asp174=
- Coding
- c.522C>T
- MANE Select
- NM_004385
- dbSNP
- rs150142826
- Type
- single nucleotide variant
- Location
- chr5:83493622 (GRCh38)
- Gene constraint
- LOEUF 0.223 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Residue 174
- the link 1 domain
Similar variants
- VCAN p.Asp174Tyr 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-asp174 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown