ACAN p.Val465=
c.1395G>A · rs2505263992 · VCV2850941
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 9e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.75 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.59 | gain · loss 0.42 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 20.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
9e-05%
European (non-Finnish) · 1/1,111,218 alleles
Overall
7.54e-05%
1/1,326,820 alleles · very rare
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
- ACAN
- Protein
- p.Val465=
- Coding
- c.1395G>A
- MANE Select
- NM_001369268
- dbSNP
- rs2505263992
- Type
- single nucleotide variant
- Location
- chr15:88845848 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
Similar variants
- ACAN p.Val465Met Uncertain significance ★★ ⚠ same residue
- ACAN p.Val465Leu Uncertain significance ★ ⚠ same residue
- ACAN c.1733-2A>G Likely pathogenic ★★ same type
- ACAN c.630-13G>A Pathogenic ★★ same type
- ACAN c.7302+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg236Ter Pathogenic ★★ same type
- ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Arg394Ter Pathogenic ★★ 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/acan-p-val465 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown