Is COMP p.Thr65= (c.195G>A) pathogenic?

COMP p.Thr65= (c.195G>A) is classified Benign in COMP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-18). Rare (popmax 0.569%, sas); Associated with pseudoachondroplasia.

What condition is associated with COMP p.Thr65= (c.195G>A)?

COMP p.Thr65= (c.195G>A) is associated with pseudoachondroplasia, multiple epiphyseal dysplasia type 1 (ClinVar).

How common is COMP p.Thr65= (c.195G>A) in the general population?

COMP p.Thr65= (c.195G>A) is rare (popmax 0.569%, sas) (gnomAD).

How is Pseudoachondroplasia inherited?

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

COMP p.Thr65=

c.195G>A · rs529891904 · VCV328628

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.569%, sas)

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 -4.8	GERP -4
Overall
CADD	9.816	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.569% South Asian · 518/91,082 alleles

Filtering AF 0.528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.512%

Overall 0.0347% 560/1,613,942 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.569%	176
Remaining individualsnot grpmax-eligible	0.056%	1,786
Middle Eastern	0.033%	3,031
East Asian	0.00669%	14,953
European (non-Finnish)	0.00017%	589,943

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.Thr65=
Coding: c.195G>A
MANE Select: NM_000095
dbSNP: rs529891904
Type: single nucleotide variant
Location: chr19:18790584 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 65: the 'comp n-terminal' region

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: 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 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-p-thr65 (accessed [today's date]).

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