Is COPA p.Asn121= (c.363C>T) pathogenic?

COPA p.Asn121= (c.363C>T) is classified Benign/Likely benign in COPA (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 86.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Asn121= (c.363C>T)?

COPA p.Asn121= (c.363C>T) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

COPA p.Asn121=

Q: How common is COPA p.Asn121= (c.363C>T) in the general population?

COPA p.Asn121= (c.363C>T) is common (popmax 86.5%, 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.

c.363C>T · rs1802778 · VCV1167833

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 86.5%, 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -3.3, phastCons 1
Overall
CADD	1.93	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 86.5% African / African-American · 64,837/74,920 alleles

Filtering AF 86% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.8%

Overall 56.4% 907,849/1,609,418 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	86.5%	1
South Asian	68.3%	1
Middle Eastern	61.5%	2
Remaining individualsnot grpmax-eligible	56.8%	2
Admixed American	55.9%	2
Amishnot grpmax-eligible	55.3%	2
European (non-Finnish)	54.4%	2
Finnishnot grpmax-eligible	51.9%	2
Ashkenazi Jewishnot grpmax-eligible	47.1%	2
East Asian	46.5%	2

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.Asn121=
Coding: c.363C>T
MANE Select: NM_004371
dbSNP: rs1802778
Type: single nucleotide variant
Location: chr1:160333626 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 121: a β-strand

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-p-asn121 (accessed [today's date]).

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