Is COMP p.Ser459del (c.1375_1377del) pathogenic?

COMP p.Ser459del (c.13751377del) is classified Pathogenic in COMP (ClinVar, No assertion criteria, 1 submitter; last evaluated 1995-07-01). No gnomAD frequency available for this variant; Associated with pseudoachondroplasia.

What condition is associated with COMP p.Ser459del (c.1375_1377del)?

COMP p.Ser459del (c.1375_1377del) is associated with pseudoachondroplasia (ClinVar).

How common is COMP p.Ser459del (c.1375_1377del) in the general population?

COMP p.Ser459del (c.1375_1377del) 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.Ser459del

c.1375_1377del · rs2145900868 · VCV9185

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

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 7.6	GERP 2, phastCons 1

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.Ser459del
Coding: c.1375_1377del
MANE Select: NM_000095
dbSNP: rs2145900868
Type: Deletion
Location: chr19:18786077 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 459: a UniProt-annotated variant site (in psach; severe form); the 'disordered' region

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

For Pseudoachondroplasia (Orphanet):

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

Similar variants

COMP p.Ser459Pro Uncertain significance ★★ ⚠ same residue
COMP p.Asn474_Asp475del Likely pathogenic ★ same condition
COMP c.917_976-68del Pathogenic same condition
COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp273Val Likely pathogenic ★★ same condition
COMP p.Asp349His Pathogenic ★★ same condition
COMP p.Asp374del Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp385Asn 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-ser459del (accessed [today's date]).

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