Is COPA p.Thr99= (c.297G>A) pathogenic?

COPA p.Thr99= (c.297G>A) is classified Benign in COPA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-31). Low-frequency (popmax 3.21%, eas); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Thr99= (c.297G>A)?

COPA p.Thr99= (c.297G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Thr99= (c.297G>A) in the general population?

COPA p.Thr99= (c.297G>A) is low-frequency (popmax 3.21%, eas) (gnomAD).

COPA p.Thr99=

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.297G>A · rs77097084 · VCV476027

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.21%, eas)

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 -15	GERP -4.6
Overall
CADD	0.344	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.21% East Asian · 1,430/44,538 alleles

Filtering AF 3.07% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.02%

Overall 0.162% 2,600/1,608,976 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	3.21%	31
Admixed American	1.52%	66
Remaining individualsnot grpmax-eligible	0.13%	768
African / African-American	0.0722%	1,385
South Asian	0.061%	1,639
Middle Eastern	0.0165%	6,052
European (non-Finnish)	0.00611%	16,354

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.Thr99=
Coding: c.297G>A
MANE Select: NM_004371
dbSNP: rs77097084
Type: single nucleotide variant
Location: chr1:160335254 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 99: 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.Thr99Ala Uncertain significance ★★ ⚠ same residue
COPA p.Thr99Met Conflicting classifications of pathogenicity ★ ⚠ 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

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-thr99 (accessed [today's date]).

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