Is COMP p.Asn652= (c.1956C>T) pathogenic?

COMP p.Asn652= (c.1956C>T) is classified Benign/Likely benign in COMP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-11). Low-frequency (popmax 2.73%, afr); Associated with pseudoachondroplasia.

What condition is associated with COMP p.Asn652= (c.1956C>T)?

COMP p.Asn652= (c.1956C>T) is associated with pseudoachondroplasia, connective tissue disorder, multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP p.Asn652= (c.1956C>T) in the general population?

COMP p.Asn652= (c.1956C>T) is low-frequency (popmax 2.73%, afr) (gnomAD).

How is Pseudoachondroplasia inherited?

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

COMP p.Asn652=

c.1956C>T · rs10421797 · VCV777452

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.73%, afr)

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 -6.8	GERP -4
Overall
CADD	0.141	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.73% African / African-American · 2,049/75,034 alleles

Filtering AF 2.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.59%

Overall 0.152% 2,458/1,614,072 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.73%	37
Remaining individualsnot grpmax-eligible	0.222%	450
Admixed American	0.132%	760
Middle Eastern	0.0661%	1,514
European (non-Finnish)	0.0148%	6,743
South Asian	0.00988%	10,120
East Asian	0.00668%	14,960

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.Asn652=
Coding: c.1956C>T
MANE Select: NM_000095
dbSNP: rs10421797
Type: single nucleotide variant
Location: chr19:18784322 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 652: the tsp c-terminal domain; the 'mediates cell survival and induction of the iap family of survival proteins' region; an α-helix; 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.Asn652Asp Uncertain significance ★ ⚠ 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
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

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-asn652 (accessed [today's date]).

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