Is COMP p.Thr529= (c.1587C>T) pathogenic?

COMP p.Thr529= (c.1587C>T) is classified Likely benign in COMP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-17). Very rare (popmax 0.00483%, nfe); Associated with COMP-related disorder.

What condition is associated with COMP p.Thr529= (c.1587C>T)?

COMP p.Thr529= (c.1587C>T) is associated with COMP-related disorder (ClinVar).

How common is COMP p.Thr529= (c.1587C>T) in the general population?

COMP p.Thr529= (c.1587C>T) is very rare (popmax 0.00483%, nfe) (gnomAD).

COMP p.Thr529=

c.1587C>T · rs1001694143 · VCV3040220

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00483%, nfe)

Conditions

COMP-related disorder

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 -7.5	GERP -4
Overall
CADD	2.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00483% European (non-Finnish) · 57/1,180,036 alleles

Filtering AF 0.00377% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00366% 59/1,613,362 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00483%	20,702
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,088

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.Thr529=
Coding: c.1587C>T
MANE Select: NM_000095
dbSNP: rs1001694143
Type: single nucleotide variant
Location: chr19:18785754 (GRCh38)
Gene constraint: LOEUF 1.073 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 88.60 · 1 PDB
Residue 529: a UniProt-annotated variant site (in psach); the 'mediates cell survival and induction of the iap family of survival proteins' region; a disulfide bond

Full COMP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

COMP-related disorder

Similar variants

COMP p.Thr529Ala Likely pathogenic ★ same residue
COMP p.Thr529Asn Likely pathogenic ★ same residue
COMP p.Thr529Ile Uncertain significance ★ ⚠ same residue
COMP p.Asn489Lys Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp326Asn Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp401Asn Pathogenic ★★ same condition
COMP p.Asp458Gly Pathogenic/Likely pathogenic ★★ same condition
COMP p.Asp507Gly 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-thr529 (accessed [today's date]).

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