Is COMP p.Asp374del (c.1114GAC[2]) pathogenic?

COMP p.Asp374del (c.1114GAC[2]) is classified Pathogenic/Likely pathogenic in COMP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-11-22). No gnomAD frequency available for this variant; Associated with pseudoachondroplasia.

What condition is associated with COMP p.Asp374del (c.1114GAC[2])?

COMP p.Asp374del (c.1114GAC[2]) is associated with pseudoachondroplasia, multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP p.Asp374del (c.1114GAC[2]) in the general population?

COMP p.Asp374del (c.1114GAC[2]) is no gnomAD frequency available for this variant (gnomAD).

How is Pseudoachondroplasia inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

COMP p.Asp374del

c.1114GAC[2] · rs1198060288 · VCV1404680

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pseudoachondroplasia

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 0.28	GERP -2.1, phastCons 0.99

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Asp374del
Coding: c.1114GAC[2]
MANE Select: NM_000095
dbSNP: rs1198060288
Type: Microsatellite
Location: chr19:18787504 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 374: the 'disordered' region; a UniProt-annotated variant site (in edm1); a UniProt-annotated variant site (in psach; mild form)

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

Disease context

pseudoachondroplasia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple epiphyseal dysplasia type 1

For Pseudoachondroplasia (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

COMP p.Asp374_Ile375insAsp Uncertain significance ★ same residue
COMP p.Asp473del Pathogenic ★★ same condition
COMP p.Asp473dup Pathogenic/Likely pathogenic ★★ same condition
COMP p.Glu457del Pathogenic/Likely pathogenic ★★ same condition
COMP p.Gly320_Val321insAspGly Likely pathogenic ★ same condition
COMP p.Asp471_Asp473del Uncertain significance ★ same condition
COMP p.Asp472_Asp473dup Pathogenic/Likely pathogenic same condition
COMP p.Arg718Trp 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-asp374del (accessed [today's date]).

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