Is COPA p.Gly844Asp (c.2531G>A) pathogenic?

COPA p.Gly844Asp (c.2531G>A) is classified Conflicting classifications of pathogenicity in COPA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-18). AlphaMissense: likely pathogenic (0.7412); Rare (popmax 0.138%, amr); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Gly844Asp (c.2531G>A)?

COPA p.Gly844Asp (c.2531G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome, autoinflammation and autoimmunity with immune dysregulation 1 (ClinVar).

How common is COPA p.Gly844Asp (c.2531G>A) in the general population?

COPA p.Gly844Asp (c.2531G>A) is rare (popmax 0.138%, amr) (gnomAD).

What do computational predictors say about COPA p.Gly844Asp (c.2531G>A)?

AlphaMissense predicts likely pathogenic (score 0.7412) — an in-silico prediction, not a clinical call.

COPA p.Gly844Asp

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.2531G>A · rs143115096 · VCV476025

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.7412 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.138%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
AlphaMissense	0.7412	likely pathogenic
REVEL	0.272	benign-leaning
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.138% Admixed American · 83/59,992 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.105%

Overall 0.0662% 1,069/1,614,022 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.138%	723
European (non-Finnish)	0.0788%	1,269
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Finnishnot grpmax-eligible	0.00937%	10,673
South Asian	0.00878%	11,385
African / African-American	0.00801%	12,485

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.Gly844Asp
Coding: c.2531G>A
MANE Select: NM_004371
dbSNP: rs143115096
Type: single nucleotide variant
Location: chr1:160294803 (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

Also linked: autoinflammation and autoimmunity with immune dysregulation 1

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-gly844asp (accessed [today's date]).

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