Is COPA p.Glu884del (c.2646AGA[2]) pathogenic?

COPA p.Glu884del (c.2646AGA[2]) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-06). Ultra-rare (popmax 0.0267%, amr); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Glu884del (c.2646AGA[2])?

COPA p.Glu884del (c.2646AGA[2]) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Glu884del (c.2646AGA[2]) in the general population?

COPA p.Glu884del (c.2646AGA[2]) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

COPA p.Glu884del

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.2646AGA[2] · rs778904236 · VCV1428318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

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 1.6	GERP -1.1, phastCons 1
Overall
CADD	19.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,012 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00143% 23/1,614,028 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,751
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asian	0.0011%	91,070
European (non-Finnish)	0.000424%	235,995

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.Glu884del
Coding: c.2646AGA[2]
MANE Select: NM_004371
dbSNP: rs778904236
Type: Microsatellite
Location: chr1:160294506 (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.Glu884Asp Uncertain significance ★★ ⚠ same residue
COPA p.835ID[1] Uncertain significance ★ same condition
COPA p.Gly829del Uncertain significance ★ same condition
COPA p.Phe457del Uncertain significance ★ same condition
COPA c.1443-7_1443-4del Likely benign ★ same condition
COPA c.2677-24_2677-18del Likely benign ★ same condition
COPA c.3616-12_3616-9del Likely benign ★ same condition
COPA p.Arg233His 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/copa-p-glu884del (accessed [today's date]).

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