COMP p.Asn453fs
c.1359del · VCV3066042
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
multiple epiphyseal dysplasia type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 13 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 7.8 | GERP 2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- COMP
- Protein
- p.Asn453fs
- Coding
- c.1359del
- MANE Select
- NM_000095
- Type
- Deletion
- Location
- chr19:18786095 (GRCh38)
- Gene constraint
- LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 88.60 · 1 PDB
- Residue 453
- a UniProt-annotated variant site (in edm1; fairbank type); the 'disordered' region; a disulfide bond
Disease context
multiple epiphyseal dysplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Multiple epiphyseal dysplasia type 1 (Orphanet):
- Inheritance
- Autosomal dominant
- Onset
- Childhood
Similar variants
- COMP p.Asn453Ile Likely pathogenic ★ same residue
- COMP p.Asn453Lys Pathogenic ★ same residue
- COMP p.Asn453Thr Likely pathogenic ★ same residue
- COMP p.Asn453Ser Pathogenic ⚠ same residue
- COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asn523Lys Pathogenic/Likely pathogenic ★★ same condition
- COMP p.Asn555Lys 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/comp-p-asn453fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown