Is COPA p.Asp868del (c.2598_2600del) pathogenic?

COPA p.Asp868del (c.25982600del) is classified Uncertain significance in COPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-08-06). Ultra-rare (popmax 0.0713%, eas); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Asp868del (c.2598_2600del)?

COPA p.Asp868del (c.2598_2600del) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Asp868del (c.2598_2600del) in the general population?

COPA p.Asp868del (c.2598_2600del) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

COPA p.Asp868del

Q: How is Autoimmune interstitial lung disease-arthritis syndrome inherited?

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

c.2598_2600del · rs745932575 · VCV2732490

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.36	GERP -2.1, phastCons 0.67
Overall
CADD	18.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0713% East Asian · 32/44,886 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00198% 32/1,614,206 alleles · ultra-rare

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: COPA
Protein: p.Asp868del
Coding: c.2598_2600del
MANE Select: NM_004371
dbSNP: rs745932575
Type: Deletion
Location: chr1:160294560 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB

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

Disease context

autoimmune interstitial lung disease-arthritis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autoimmune interstitial lung disease-arthritis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood, Infancy

Similar variants

COPA p.Asp868Asn Uncertain significance ★ ⚠ same residue
COPA c.387-8del Benign/Likely benign ★★ same condition
COPA p.Gln1045fs Uncertain significance ★ same condition
COPA p.Ile1218fs Uncertain significance ★ same condition
COPA p.Pro1194fs Uncertain significance ★ same condition
COPA p.Pro174del Uncertain significance ★ same condition
COPA c.154+19del Likely benign ★ same condition
COPA c.2263+9_2263+16del Likely benign ★ 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/copa-p-asp868del (accessed [today's date]).

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