Is COPA c.40+17G>C pathogenic?

COPA c.40+17G>C is classified Benign in COPA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Common (popmax 5.56%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA c.40+17G>C?

COPA c.40+17G>C is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

COPA c.40+17G>C

Q: How common is COPA c.40+17G>C in the general population?

COPA c.40+17G>C is common (popmax 5.56%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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

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

rs7555490 · VCV1165189

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.56%, afr) — too common for a highly-penetrant pathogenic allele

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 +17	near-intronic (+17 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -4.3
Overall
CADD	2.259	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.56% African / African-American · 4,171/74,980 alleles

Filtering AF 5.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.36%

Overall 0.299% 4,829/1,614,102 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.56%	18
Admixed American	0.445%	225
Remaining individualsnot grpmax-eligible	0.443%	226
Middle Eastern	0.379%	264
South Asian	0.0253%	3,960
European (non-Finnish)	0.00576%	17,353

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.40+17G>C
MANE Select: NM_004371
dbSNP: rs7555490
Type: single nucleotide variant
Location: chr1:160343114 (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-40-plus-17g-c (accessed [today's date]).

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