Is COPA p.Pro1194fs (c.3581_3582del) pathogenic?

COPA p.Pro1194fs (c.35813582del) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Pro1194fs (c.3581_3582del)?

COPA p.Pro1194fs (c.3581_3582del) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

COPA p.Pro1194fs

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.3581_3582del · VCV4733146

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (32 of 33, 33 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1

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

Variant & gene context

Gene: COPA
Protein: p.Pro1194fs
Coding: c.3581_3582del
MANE Select: NM_004371
Type: Deletion
Location: chr1:160290525 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 1194: 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 p.Asp868del Uncertain significance ★★ same condition
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.Pro174del Uncertain significance ★ same condition
COPA c.154+19del Likely benign ★ same condition
COPA c.2263+9_2263+16del Likely benign ★ same condition
COPA c.2755-16_2755-13del 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-pro1194fs (accessed [today's date]).

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