Is COPA p.Ile1218fs (c.3654_3655del) pathogenic?

COPA p.Ile1218fs (c.36543655del) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-17). Absent from gnomAD; Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Ile1218fs (c.3654_3655del)?

COPA p.Ile1218fs (c.3654_3655del) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Ile1218fs (c.3654_3655del) in the general population?

COPA p.Ile1218fs (c.3654_3655del) is absent from gnomAD (gnomAD).

COPA p.Ile1218fs

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.3654_3655del · rs2525341626 · VCV2717946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 in the last exon (33 of 33) — 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 2.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COPA
Protein: p.Ile1218fs
Coding: c.3654_3655del
MANE Select: NM_004371
dbSNP: rs2525341626
Type: Deletion
Location: chr1:160290177 (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.Ile1218Thr Uncertain significance ★ ⚠ same residue
COPA p.Ile1218Val Uncertain significance ★ ⚠ same residue
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.Pro1194fs Uncertain significance ★ same condition
COPA p.Pro174del Uncertain significance ★ same condition
COPA c.154+19del 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-ile1218fs (accessed [today's date]).

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