Is COMP c.867+11G>A pathogenic?

COMP c.867+11G>A is classified Conflicting classifications of pathogenicity in COMP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-03-23). Very rare (popmax 0.0079%, nfe); Associated with multiple epiphyseal dysplasia type 1.

What condition is associated with COMP c.867+11G>A?

COMP c.867+11G>A is associated with multiple epiphyseal dysplasia type 1, pseudoachondroplasia (ClinVar).

How common is COMP c.867+11G>A in the general population?

COMP c.867+11G>A is very rare (popmax 0.0079%, nfe) (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.867+11G>A

rs776412620 · VCV328617

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0079%, nfe)

Conditions

multiple epiphyseal dysplasia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +11	near-intronic (+11 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.7	GERP -3.7
Non-coding constraint	Z 4.74	1 kb window · o/e 0.66 · regional · uncalibrated
Overall
CADD	0.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0079% European (non-Finnish) · 93/1,176,970 alleles

Filtering AF 0.00658% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0061%

Overall 0.00629% 101/1,605,486 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0079%	12,656
Admixed American	0.0067%	14,928
Remaining individualsnot grpmax-eligible	0.00643%	15,549

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COMP
Coding: c.867+11G>A
MANE Select: NM_000095
dbSNP: rs776412620
Type: single nucleotide variant
Location: chr19:18788399 (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-867-plus-11g-a (accessed [today's date]).

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