Is COPA p.Ser402Phe (c.1205C>T) pathogenic?

COPA p.Ser402Phe (c.1205C>T) is classified Likely benign in COPA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-08). AlphaMissense: ambiguous (0.4424); Very rare (popmax 0.00833%, amr); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Ser402Phe (c.1205C>T)?

COPA p.Ser402Phe (c.1205C>T) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Ser402Phe (c.1205C>T) in the general population?

COPA p.Ser402Phe (c.1205C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about COPA p.Ser402Phe (c.1205C>T)?

AlphaMissense predicts ambiguous (score 0.4424) — an in-silico prediction, not a clinical call.

COPA p.Ser402Phe

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.1205C>T · rs200604416 · VCV970082

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4424 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

autoimmune interstitial lung disease-arthritis syndrome

Computational evidence

Protein change
AlphaMissense	0.4424	ambiguous
REVEL	0.498	indeterminate
SaProt	LLR -9.70	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	28.7	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 0.00833% Admixed American · 5/59,994 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00412%

Overall 0.00459% 74/1,613,468 alleles · very rare exomes 64/1,461,286 · genomes 10/152,182 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	11,999
European (non-Finnish)	0.0056%	17,871
Remaining individualsnot grpmax-eligible	0.0032%	31,235
African / African-American	0.00133%	74,914

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.Ser402Phe
Coding: c.1205C>T
MANE Select: NM_004371
dbSNP: rs200604416
Type: single nucleotide variant
Location: chr1:160309115 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 402: a modified residue (phosphoserine)

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-ser402phe (accessed [today's date]).

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