Is COPA p.Arg39Gln (c.116G>A) pathogenic?

COPA p.Arg39Gln (c.116G>A) is classified Likely benign in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-04). AlphaMissense: likely pathogenic (0.921); Very rare (popmax 0.00133%, afr); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Arg39Gln (c.116G>A)?

COPA p.Arg39Gln (c.116G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Arg39Gln (c.116G>A) in the general population?

COPA p.Arg39Gln (c.116G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about COPA p.Arg39Gln (c.116G>A)?

AlphaMissense predicts likely pathogenic (score 0.921) — an in-silico prediction, not a clinical call.

COPA p.Arg39Gln

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.116G>A · rs747408205 · VCV2178684

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.921 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
AlphaMissense	0.921	likely pathogenic
REVEL	0.706	pathogenic-leaning
SaProt	LLR -10.60	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 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 11 kb · p 2.2e-12 · regional, not allelic
Overall
CADD	32.0	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 0.00133% African / African-American · 1/74,964 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000411% 6/1,461,438 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,964
European (non-Finnish)	0.000424%	235,974

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.Arg39Gln
Coding: c.116G>A
MANE Select: NM_004371
dbSNP: rs747408205
Type: single nucleotide variant
Location: chr1:160340219 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 39: a turn

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.Arg39Trp Uncertain significance ★ ⚠ same residue
COPA p.Arg39= Likely benign ★ same residue
COPA p.Arg39Leu Uncertain significance ★ ⚠ 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

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-arg39gln (accessed [today's date]).

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