Is COPA p.Lys793Arg (c.2378A>G) pathogenic?

COPA p.Lys793Arg (c.2378A>G) is classified Conflicting classifications of pathogenicity in COPA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-05). AlphaMissense: likely benign (0.077); Rare (popmax 0.292%, eas); Associated with Inborn genetic diseases.

What condition is associated with COPA p.Lys793Arg (c.2378A>G)?

COPA p.Lys793Arg (c.2378A>G) is associated with Inborn genetic diseases, autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Lys793Arg (c.2378A>G) in the general population?

COPA p.Lys793Arg (c.2378A>G) is rare (popmax 0.292%, eas) (gnomAD).

What do computational predictors say about COPA p.Lys793Arg (c.2378A>G)?

AlphaMissense predicts likely benign (score 0.077) — an in-silico prediction, not a clinical call.

COPA p.Lys793Arg

c.2378A>G · rs201804449 · VCV2162616

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.077 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.292%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.077	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.26	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 1.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	18.33	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 0.292% East Asian · 131/44,882 alleles

Filtering AF 0.251% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.236%

Overall 0.00843% 136/1,612,702 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.292%	343
Remaining individualsnot grpmax-eligible	0.0048%	20,817
South Asian	0.0011%	90,706
European (non-Finnish)	8.48e-05%	1,179,600

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.Lys793Arg
Coding: c.2378A>G
MANE Select: NM_004371
dbSNP: rs201804449
Type: single nucleotide variant
Location: chr1:160295834 (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

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.Lys793= Likely benign ★★ same residue
COPA p.Lys793Asn Conflicting classifications of pathogenicity ★ same residue
COPA p.Lys793Glu Conflicting classifications of pathogenicity ★ ⚠ 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-lys793arg (accessed [today's date]).

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