ACAN p.Ser1411=
c.4233C>T · VCV3898236
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, amr)
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 -20 | GERP -1.8 |
| Overall | ||
| CADD | 0.206 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
Admixed American · 10/56,970 alleles
Filtering AF
0.00944%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00724%
Overall
0.00232%
36/1,550,908 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0176% | 5,697 |
| Remaining individualsnot grpmax-eligible | 0.00841% | 11,894 |
| African / African-American | 0.00757% | 13,216 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00361% | 27,690 |
| Finnishnot grpmax-eligible | 0.00168% | 59,592 |
| South Asian | 0.00115% | 87,302 |
| European (non-Finnish) | 0.00114% | 88,103 |
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.Ser1411=
- Coding
- c.4233C>T
- MANE Select
- NM_001369268
- Type
- single nucleotide variant
- Location
- chr15:88856818 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 1411
- the 'cs-1' region; the '35 x 19 aa approximate tandem repeats of e-[ivdg]-[lv]-[ev]-[gti]-[sta]-[atv]-[sp]-[ga]-[vifad]-[gedl]-[de]-[lvi]-[sg]-[gerk]-[lv]-p-s-g' region
Similar variants
- 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
- ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same type
- ACAN p.Asp2419Asn Likely 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-ser1411 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown