Is COPA p.Gln479= (c.1437G>A) pathogenic?

COPA p.Gln479= (c.1437G>A) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-31). Very rare (popmax 8.51e-05%, nfe); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Gln479= (c.1437G>A)?

COPA p.Gln479= (c.1437G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Gln479= (c.1437G>A) in the general population?

COPA p.Gln479= (c.1437G>A) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

COPA p.Gln479=

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.1437G>A · rs1658785537 · VCV3007491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	donor loss, 17 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.6	GERP 0.59, phastCons 1
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.51e-05% European (non-Finnish) · 1/1,174,500 alleles

Overall 6.24e-05% 1/1,603,478 alleles · very rare exomes 0/1,451,256 · genomes 1/152,222 · joint denominator

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.Gln479=
Coding: c.1437G>A
MANE Select: NM_004371
dbSNP: rs1658785537
Type: single nucleotide variant
Location: chr1:160306359 (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.Arg233His Pathogenic/Likely pathogenic ★★ same condition
COPA p.Glu241Lys Pathogenic ★★ same condition
COPA p.Ala111Thr Uncertain significance ★★ ⚠ same condition
COPA p.Ala176Val Uncertain significance ★★ ⚠ same condition
COPA p.Ala407Val Uncertain significance ★★ ⚠ same condition
COPA p.Ala422Thr Uncertain significance ★★ ⚠ same condition
COPA p.Ala469Val Uncertain significance ★★ ⚠ same condition
COPA p.Ala510Thr Uncertain significance ★★ ⚠ 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-gln479 (accessed [today's date]).

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