Is COPA p.Asn686Thr (c.2057A>C) pathogenic?

COPA p.Asn686Thr (c.2057A>C) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-18). AlphaMissense: likely pathogenic (0.8768); Absent from gnomAD v4.1; Associated with autoinflammation and autoimmunity with immune dysregulation 1.

What condition is associated with COPA p.Asn686Thr (c.2057A>C)?

COPA p.Asn686Thr (c.2057A>C) is associated with autoinflammation and autoimmunity with immune dysregulation 1 (ClinVar).

How common is COPA p.Asn686Thr (c.2057A>C) in the general population?

COPA p.Asn686Thr (c.2057A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPA p.Asn686Thr (c.2057A>C)?

AlphaMissense predicts likely pathogenic (score 0.8768) — an in-silico prediction, not a clinical call.

COPA p.Asn686Thr

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.2057A>C · VCV4855024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8768 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoinflammation and autoimmunity with immune dysregulation 1

Computational evidence

Protein change
AlphaMissense	0.8768	likely pathogenic
REVEL	0.653	pathogenic-leaning
SaProt	LLR -13.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COPA
Protein: p.Asn686Thr
Coding: c.2057A>C
MANE Select: NM_004371
Type: single nucleotide variant
Location: chr1:160297666 (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

autoinflammation and autoimmunity with immune dysregulation 1 — 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.Asn686Lys Uncertain significance ★ ⚠ same residue
COPA p.Glu241Lys Pathogenic ★★ same condition
COPA p.Gly247Asp Uncertain significance ★ ⚠ same condition
COPA p.Gly844Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
COPA p.Ala407Pro Likely benign ★ same condition
COPA c.1978-2_1978-1insAAA Uncertain significance ★ same condition
COPA p.Arg233His Pathogenic/Likely pathogenic ★★ same type
COPA p.Ala111Thr Uncertain significance ★★ ⚠ same type

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-asn686thr (accessed [today's date]).

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