Is COPA p.Ser1172= (c.3516A>G) pathogenic?

COPA p.Ser1172= (c.3516A>G) is classified Likely benign in COPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-23). Very rare (popmax 0.00167%, amr); Associated with autoimmune interstitial lung disease-arthritis syndrome.

What condition is associated with COPA p.Ser1172= (c.3516A>G)?

COPA p.Ser1172= (c.3516A>G) is associated with autoimmune interstitial lung disease-arthritis syndrome (ClinVar).

How common is COPA p.Ser1172= (c.3516A>G) in the general population?

COPA p.Ser1172= (c.3516A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

COPA p.Ser1172=

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.3516A>G · rs761026418 · VCV2900925

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.16	GERP -5.7, phastCons 0.006
Overall
CADD	4.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,994 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.0013% 21/1,614,076 alleles · very rare exomes 20/1,461,890 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,994
European (non-Finnish)	0.00161%	62,108
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Ser1172=
Coding: c.3516A>G
MANE Select: NM_004371
dbSNP: rs761026418
Type: single nucleotide variant
Location: chr1:160290591 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 1172: a turn

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-ser1172 (accessed [today's date]).

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