Is COPA p.Ala1048fs (c.3141dup) pathogenic?

COPA p.Ala1048fs (c.3141dup) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Ala1048fs (c.3141dup)?

COPA p.Ala1048fs (c.3141dup) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

COPA p.Ala1048fs

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.3141dup · VCV3649958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 29 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.5	GERP 2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: COPA
Protein: p.Ala1048fs
Coding: c.3141dup
MANE Select: NM_004371
Type: Duplication
Location: chr1:160292017 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 1048: an α-helix

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 c.387-17dup Benign/Likely benign ★★ same condition
COPA c.2773_2823+12dup Uncertain significance ★ same condition
COPA c.926-5_926-2dup Uncertain significance ★ same condition
COPA p.Leu357dup Uncertain significance ★ same condition
COPA c.2477-11dup Likely benign ★ same condition
COPA c.41-14dup Benign ★ same condition
COPA c.41-4dup Benign ★ same condition
COPA c.496+4_496+7dup 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-ala1048fs (accessed [today's date]).

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