Is COPA p.Arg747Gln (c.2240G>A) pathogenic?

COPA p.Arg747Gln (c.2240G>A) is classified Likely benign in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: likely benign (0.2528); Ultra-rare (popmax 0.0164%, mid); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Arg747Gln (c.2240G>A)?

COPA p.Arg747Gln (c.2240G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Arg747Gln (c.2240G>A) in the general population?

COPA p.Arg747Gln (c.2240G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about COPA p.Arg747Gln (c.2240G>A)?

AlphaMissense predicts likely benign (score 0.2528) — an in-silico prediction, not a clinical call.

COPA p.Arg747Gln

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.2240G>A · rs759567454 · VCV861362

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2528 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
AlphaMissense	0.2528	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	27.9	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00161% 26/1,613,986 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00878%	11,385
African / African-American	0.00401%	24,963
East Asian	0.00223%	44,898
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000932%	107,273

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.Arg747Gln
Coding: c.2240G>A
MANE Select: NM_004371
dbSNP: rs759567454
Type: single nucleotide variant
Location: chr1:160297366 (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.Arg747= Likely benign ★ same residue
COPA p.Arg747Trp Likely benign ★ same residue
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

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-arg747gln (accessed [today's date]).

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