Is COPA p.Val1040Ala (c.3119T>C) pathogenic?

COPA p.Val1040Ala (c.3119T>C) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: ambiguous (0.3712); Absent from gnomAD v4.1; Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Val1040Ala (c.3119T>C)?

COPA p.Val1040Ala (c.3119T>C) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Val1040Ala (c.3119T>C) in the general population?

COPA p.Val1040Ala (c.3119T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPA p.Val1040Ala (c.3119T>C)?

AlphaMissense predicts ambiguous (score 0.3712) — an in-silico prediction, not a clinical call.

COPA p.Val1040Ala

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.3119T>C · rs34997807 · VCV1719225

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3712 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
AlphaMissense	0.3712	ambiguous
REVEL	0.325	indeterminate
SaProt	LLR -10.79	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COPA
Protein: p.Val1040Ala
Coding: c.3119T>C
MANE Select: NM_004371
dbSNP: rs34997807
Type: single nucleotide variant
Location: chr1:160292040 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 1040: a UniProt-annotated variant site (in)

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-val1040ala (accessed [today's date]).

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