ACAN p.Ser1644fs
c.4929del · VCV4082364
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
spondyloepiphyseal dysplasia, Kimberley type
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 12 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -1.2 | GERP -2 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ACAN
- Protein
- p.Ser1644fs
- Coding
- c.4929del
- MANE Select
- NM_001369268
- Type
- Deletion
- Location
- chr15:88857512 (GRCh38)
- Gene constraint
- LOEUF 0.377 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 53.32 · 4 PDB
- Residue 1644
- the 'disordered' region; the 'cs-2' region
Disease context
spondyloepiphyseal dysplasia, Kimberley type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Spondyloepiphyseal dysplasia, Kimberley type (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Infancy, Neonatal
Similar variants
- ACAN c.758-37del Benign ★★ same condition
- ACAN p.Ala863fs Likely pathogenic ★ same condition
- ACAN p.Ala583fs Likely pathogenic same condition
- ACAN c.1733-2A>G Likely pathogenic ★★ same condition
- ACAN p.Arg675Ter Pathogenic/Likely pathogenic ★★ same condition
- ACAN p.Gly366_Glu367insTer Pathogenic ★★ same condition
- ACAN p.Tyr164Ter Pathogenic ★★ same condition
- ACAN p.Arg279Gln Uncertain significance ★★ ⚠ 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-ser1644fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown