Is COPA c.2263+7A>G pathogenic?

COPA c.2263+7A>G is classified Benign in COPA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-23). Low-frequency (popmax 1.31%, afr); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA c.2263+7A>G?

COPA c.2263+7A>G is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA c.2263+7A>G in the general population?

COPA c.2263+7A>G is low-frequency (popmax 1.31%, afr) (gnomAD).

COPA c.2263+7A>G

Q: How is Autoimmune interstitial lung disease-arthritis syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

rs116596416 · VCV476023

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.31%, afr)

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP -3.5
Non-coding constraint	Z 3.65	1 kb window · o/e 0.74 · regional · uncalibrated
Overall
CADD	8.753	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.31% African / African-American · 979/75,016 alleles

Filtering AF 1.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.21%

Overall 0.0697% 1,124/1,613,692 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.31%	77
Remaining individualsnot grpmax-eligible	0.115%	868
Admixed American	0.09%	1,112
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.00127%	78,640
South Asian	0.0011%	91,072

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
Coding: c.2263+7A>G
MANE Select: NM_004371
dbSNP: rs116596416
Type: single nucleotide variant
Location: chr1:160297336 (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.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-c-2263-plus-7a-g (accessed [today's date]).

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