Is COPA p.Arg425= (c.1275G>T) pathogenic?

COPA p.Arg425= (c.1275G>T) is classified Likely benign in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-06). Very rare (popmax 0.00167%, amr).

How common is COPA p.Arg425= (c.1275G>T) in the general population?

COPA p.Arg425= (c.1275G>T) is very rare (popmax 0.00167%, amr) (gnomAD).

COPA p.Arg425=

c.1275G>T · VCV4918651

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 -0.21	GERP -4.9, phastCons 0.22
Overall
CADD	6.465	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,026 alleles

Overall 0.000137% 2/1,461,848 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,026
Remaining individualsnot grpmax-eligible	0.0016%	62,510

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.Arg425=
Coding: c.1275G>T
MANE Select: NM_004371
Type: single nucleotide variant
Location: chr1:160307190 (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

Similar variants

COPA p.Arg425Leu Uncertain significance ★ ⚠ same residue
COPA p.Arg425Gln Likely benign ★ same residue
COPA p.Arg233His Pathogenic/Likely pathogenic ★★ same type
COPA p.Glu241Lys Pathogenic ★★ same type
COPA p.Ala111Thr Uncertain significance ★★ ⚠ same type
COPA p.Ala176Val Uncertain significance ★★ ⚠ same type
COPA p.Ala407Val Uncertain significance ★★ ⚠ same type
COPA p.Ala422Thr Uncertain significance ★★ ⚠ same type

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-arg425 (accessed [today's date]).

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