Is COMP c.1489+2T>A pathogenic?

COMP c.1489+2T>A is classified Uncertain significance in COMP (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-12). Absent from gnomAD v4.1; Associated with multiple epiphyseal dysplasia type 1.

What condition is associated with COMP c.1489+2T>A?

COMP c.1489+2T>A is associated with multiple epiphyseal dysplasia type 1, pseudoachondroplasia (ClinVar).

How common is COMP c.1489+2T>A in the general population?

COMP c.1489+2T>A 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.

COMP c.1489+2T>A

rs1131692038 · VCV430605

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

multiple epiphyseal dysplasia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	Δ0.99	donor loss · deltas
Pangolin	Δ0.84	loss · gain 0.13 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.2	GERP 2, phastCons 1
Overall
CADD	29.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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
Coding: c.1489+2T>A
MANE Select: NM_000095
dbSNP: rs1131692038
Type: single nucleotide variant
Location: chr19:18785963 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB

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

Also linked: pseudoachondroplasia

For Multiple epiphyseal dysplasia type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

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
COMP p.Asp269Gly Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp273Val Likely pathogenic ★★ same condition
COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp349His 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-c-1489-plus-2t-a (accessed [today's date]).

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