Is COMP p.Asp439Glu (c.1317C>G) pathogenic?

COMP p.Asp439Glu (c.1317C>G) is classified Pathogenic/Likely pathogenic in COMP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-02). AlphaMissense: likely pathogenic (0.9878); Absent from gnomAD v4.1; Associated with multiple epiphyseal dysplasia type 1.

What condition is associated with COMP p.Asp439Glu (c.1317C>G)?

COMP p.Asp439Glu (c.1317C>G) is associated with multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP p.Asp439Glu (c.1317C>G) in the general population?

COMP p.Asp439Glu (c.1317C>G) is absent from gnomAD v4.1 (gnomAD).

How is Multiple epiphyseal dysplasia type 1 inherited?

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

What do computational predictors say about COMP p.Asp439Glu (c.1317C>G)?

AlphaMissense predicts likely pathogenic (score 0.9878) — an in-silico prediction, not a clinical call.

COMP p.Asp439Glu

c.1317C>G · rs368273443 · VCV1066197

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9878 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple epiphyseal dysplasia type 1

Computational evidence

Protein change
AlphaMissense	0.9878	likely pathogenic ✓ concordant with ClinVar
REVEL	0.881	moderately pathogenic-leaning
SaProt	LLR -7.15	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.8	GERP -4
Regional constraint	o/e 0.84	unconstrained · MANE · 8,351 bp · p 2.2e-07 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COMP
Protein: p.Asp439Glu
Coding: c.1317C>G
MANE Select: NM_000095
dbSNP: rs368273443
Type: single nucleotide variant
Location: chr19:18786137 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 439: the 'disordered' region

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

Disease context

multiple epiphyseal dysplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple epiphyseal dysplasia type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

COMP p.Asp439Asn Likely pathogenic ★ same residue
COMP p.Asp439Gly Likely pathogenic ★★ same residue
COMP p.Asp439Tyr Pathogenic/Likely pathogenic ★★ same residue
COMP p.Asp439Ala Uncertain significance ★ ⚠ same residue
COMP p.Asp439= Likely benign ★ 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

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-asp439glu (accessed [today's date]).

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