ACAN p.Ser509=
c.1527G>A · rs371049725 · VCV502617
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, mid)
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 -13 | GERP -3.7 |
| Overall | ||
| CADD | 0.072 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
Middle Eastern · 1/5,682 alleles
Filtering AF
0.00724%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00676%
Overall
0.00682%
108/1,584,364 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0176% | 5,682 |
| European (non-Finnish) | 0.00866% | 11,550 |
| Remaining individualsnot grpmax-eligible | 0.00652% | 15,349 |
| Admixed American | 0.00179% | 55,856 |
| African / African-American | 0.00135% | 74,266 |
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.Ser509=
- Coding
- c.1527G>A
- MANE Select
- NM_001369268
- dbSNP
- rs371049725
- Type
- single nucleotide variant
- Location
- chr15:88847340 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 509
- a disulfide bond; the link 3 domain; the 'g2-b' region
Similar variants
- ACAN p.Ser509Leu Uncertain significance ★★ ⚠ same residue
- ACAN p.Ser509Pro Uncertain significance ★ ⚠ same residue
- ACAN p.Ser509Trp Uncertain significance ★ ⚠ same residue
- ACAN p.Ser509fs Pathogenic ★★ 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
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-ser509 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown