Is COPA p.Arg1142Gln (c.3425G>A) pathogenic?

COPA p.Arg1142Gln (c.3425G>A) is classified Uncertain significance in COPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-12-05). AlphaMissense: ambiguous (0.456); Very rare (popmax 0.008%, afr); Associated with Inborn genetic diseases.

What condition is associated with COPA p.Arg1142Gln (c.3425G>A)?

COPA p.Arg1142Gln (c.3425G>A) is associated with Inborn genetic diseases, autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Arg1142Gln (c.3425G>A) in the general population?

COPA p.Arg1142Gln (c.3425G>A) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about COPA p.Arg1142Gln (c.3425G>A)?

AlphaMissense predicts ambiguous (score 0.456) — an in-silico prediction, not a clinical call.

COPA p.Arg1142Gln

c.3425G>A · rs768877876 · VCV846768

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.456 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.456	ambiguous
REVEL	0.316	indeterminate
SaProt	LLR -5.20	tolerated
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 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	31.0	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 0.008% African / African-American · 6/74,998 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00123% 18/1,461,702 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,500
East Asian	0.00223%	44,882
South Asian	0.0011%	91,068
European (non-Finnish)	0.000848%	117,993

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.Arg1142Gln
Coding: c.3425G>A
MANE Select: NM_004371
dbSNP: rs768877876
Type: single nucleotide variant
Location: chr1:160290682 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 1142: an α-helix

Full COPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autoimmune interstitial lung disease-arthritis syndrome

Similar variants

COPA p.Arg1142Ter Pathogenic 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
COPA p.Ala469Val 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-arg1142gln (accessed [today's date]).

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