Is COMP p.Arg718= (c.2152C>A) pathogenic?

COMP p.Arg718= (c.2152C>A) is classified Benign/Likely benign in COMP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Rare (popmax 0.258%, amr); Associated with pseudoachondroplasia.

What condition is associated with COMP p.Arg718= (c.2152C>A)?

COMP p.Arg718= (c.2152C>A) is associated with pseudoachondroplasia, connective tissue disorder, multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP p.Arg718= (c.2152C>A) in the general population?

COMP p.Arg718= (c.2152C>A) is rare (popmax 0.258%, amr) (gnomAD).

How is Pseudoachondroplasia inherited?

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

COMP p.Arg718=

c.2152C>A · rs28936368 · VCV769450

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.258%, amr)

Conditions

pseudoachondroplasia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.1	GERP -3.5, phastCons 0.79
Overall
CADD	5.822	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.258% Admixed American · 155/60,028 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.0976% 1,572/1,610,894 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.258%	387
European (non-Finnish)	0.114%	875
Remaining individualsnot grpmax-eligible	0.0896%	1,116
African / African-American	0.016%	6,256

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
Protein: p.Arg718=
Coding: c.2152C>A
MANE Select: NM_000095
dbSNP: rs28936368
Type: single nucleotide variant
Location: chr19:18783129 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 718: a UniProt-annotated variant site (in edm1); a UniProt-annotated variant site (in edm1 and cts2; reduced secretion in tendon cells and chondrocytes); the tsp c-terminal domain; the 'mediates cell survival and induction of the iap family of survival proteins' region; a β-strand; a disulfide bond

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: connective tissue disorder multiple epiphyseal dysplasia type 1

For Pseudoachondroplasia (Orphanet):

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

Similar variants

COMP p.Arg718Trp Pathogenic/Likely pathogenic ★★ ⚠ same residue
COMP p.Arg718Pro Pathogenic ★ same residue
COMP p.Arg718Gln Uncertain significance ★ ⚠ same residue
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

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-arg718 (accessed [today's date]).

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