ACAN p.Ser540fs
c.1620_1621delinsG · VCV4850013
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
Autosomal dominant ACAN-related disorders
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 9 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.57 | GERP -1.6, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ACAN
- Protein
- p.Ser540fs
- Coding
- c.1620_1621delinsG
- MANE Select
- NM_001369268
- Type
- Indel
- Location
- chr15:88847926 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 540
- a disulfide bond; the link 3 domain; the 'g2-b' region
Disease context
Autosomal dominant ACAN-related disorders
Similar variants
- ACAN p.Ser540Asn Uncertain significance ★★ ⚠ same residue
- ACAN p.Asn2446fs Likely pathogenic ★ same condition
- ACAN c.630-13G>A Pathogenic ★★ same condition
- ACAN p.Arg236Ter Pathogenic ★★ same condition
- ACAN p.Arg386Ter Pathogenic/Likely pathogenic ★★ same condition
- ACAN p.Arg394Ter Pathogenic ★★ same condition
- ACAN p.Asn108fs Pathogenic/Likely pathogenic ★★ same condition
- ACAN p.Cys2304Ter Pathogenic/Likely pathogenic ★★ same condition
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-ser540fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown