Is COPA p.Leu581= (c.1741C>T) pathogenic?

COPA p.Leu581= (c.1741C>T) is classified Benign/Likely benign in COPA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-31). Low-frequency (popmax 3.49%, nfe); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Leu581= (c.1741C>T)?

COPA p.Leu581= (c.1741C>T) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Leu581= (c.1741C>T) in the general population?

COPA p.Leu581= (c.1741C>T) is low-frequency (popmax 3.49%, nfe) (gnomAD).

COPA p.Leu581=

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.1741C>T · rs79304843 · VCV476022

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.49%, 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
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Overall
CADD	11.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.49% European (non-Finnish) · 41,183/1,180,004 alleles

Filtering AF 3.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.45%

Overall 3.11% 50,227/1,614,114 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.49%	29
Middle Eastern	3.23%	31
South Asian	3.17%	32
Ashkenazi Jewishnot grpmax-eligible	2.86%	35
Remaining individualsnot grpmax-eligible	2.84%	35
Amishnot grpmax-eligible	2.19%	46
Finnishnot grpmax-eligible	1.95%	51
Admixed American	1.63%	61
African / African-American	1.45%	69
East Asian	0.0111%	8,977

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.Leu581=
Coding: c.1741C>T
MANE Select: NM_004371
dbSNP: rs79304843
Type: single nucleotide variant
Location: chr1:160299191 (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.Leu581Gln Likely pathogenic ★ 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
COPA p.Ala422Thr Uncertain significance ★★ ⚠ same condition
COPA p.Ala469Val 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-leu581 (accessed [today's date]).

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