Is COPA c.3147+16C>T pathogenic?

COPA c.3147+16C>T is classified Likely benign in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-01). Ultra-rare (popmax 0.02%, nfe); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA c.3147+16C>T?

COPA c.3147+16C>T is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA c.3147+16C>T in the general population?

COPA c.3147+16C>T is ultra-rare (popmax 0.02%, nfe) (gnomAD).

COPA c.3147+16C>T

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

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

rs576052309 · VCV1160766

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, nfe)

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 +16	near-intronic (+16 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.74	GERP -5.6
Non-coding constraint	Z 4.00	1 kb window · o/e 0.71 · regional · uncalibrated
Overall
CADD	1.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% European (non-Finnish) · 236/1,179,992 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0161% 260/1,614,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.02%	5,000
Remaining individualsnot grpmax-eligible	0.0112%	8,929
Finnishnot grpmax-eligible	0.0109%	9,147
African / African-American	0.00933%	10,718
South Asian	0.0022%	45,539
Admixed American	0.00167%	60,014

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.3147+16C>T
MANE Select: NM_004371
dbSNP: rs576052309
Type: single nucleotide variant
Location: chr1:160291996 (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-3147-plus-16c-t (accessed [today's date]).

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