Is COPA p.Ala898Thr (c.2692G>A) pathogenic?

COPA p.Ala898Thr (c.2692G>A) is classified Conflicting classifications of pathogenicity in COPA (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0665); Very rare (popmax 0.00331%, nfe); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Ala898Thr (c.2692G>A)?

COPA p.Ala898Thr (c.2692G>A) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Ala898Thr (c.2692G>A) in the general population?

COPA p.Ala898Thr (c.2692G>A) is very rare (popmax 0.00331%, nfe) (gnomAD).

What do computational predictors say about COPA p.Ala898Thr (c.2692G>A)?

AlphaMissense predicts likely benign (score 0.0665) — an in-silico prediction, not a clinical call.

COPA p.Ala898Thr

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.2692G>A · rs750545966 · VCV1905738

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0665 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
AlphaMissense	0.0665	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 1.8, phastCons 0.18
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	16.19	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00331% European (non-Finnish) · 39/1,176,656 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00218%

Overall 0.00283% 41/1,451,000 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,171
African / African-American	0.00135%	74,088
South Asian	0.00112%	88,998

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.Ala898Thr
Coding: c.2692G>A
MANE Select: NM_004371
dbSNP: rs750545966
Type: single nucleotide variant
Location: chr1:160293448 (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.Ala898Glu Uncertain significance ★ ⚠ 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-ala898thr (accessed [today's date]).

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