Is COMP p.Asp473del (c.1405GAC[4]) pathogenic?

COMP p.Asp473del (c.1405GAC[4]) is classified Pathogenic in COMP (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-03-10). Absent from gnomAD v4.1; Associated with COMP-related disorder.

What condition is associated with COMP p.Asp473del (c.1405GAC[4])?

COMP p.Asp473del (c.1405GAC[4]) is associated with COMP-related disorder, multiple epiphyseal dysplasia type 1, pseudoachondroplasia (ClinVar).

How common is COMP p.Asp473del (c.1405GAC[4]) in the general population?

COMP p.Asp473del (c.1405GAC[4]) is absent from gnomAD v4.1 (gnomAD).

COMP p.Asp473del

c.1405GAC[4] · rs193922900 · VCV40988

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,658)

Conditions

COMP-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 1.1, phastCons 1
Region caveats
Repeat context	tandem	(CGT)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,658). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COMP
Protein: p.Asp473del
Coding: c.1405GAC[4]
MANE Select: NM_000095
dbSNP: rs193922900
Type: Microsatellite
Location: chr19:18786035 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 473: a UniProt-annotated variant site (in edm1); a UniProt-annotated variant site (in psach; severe form); a UniProt-annotated variant site (in psach); a β-strand; the 'disordered' region

Full COMP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COMP-related disorder

Also linked: multiple epiphyseal dysplasia type 1 pseudoachondroplasia

Similar variants

COMP p.Asp473dup Pathogenic/Likely pathogenic ★★ same residue
COMP p.Asp473His Likely pathogenic ★ same residue
COMP p.Asp473Gly Pathogenic same residue
COMP p.Asp374del Pathogenic/Likely pathogenic ★★ same condition
COMP p.Glu457del Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp473Asn Likely pathogenic ★ same residue
COMP p.Gly320_Val321insAspGly Likely pathogenic ★ same condition
COMP p.Asp471_Asp473del 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/comp-p-asp473del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown