Is COPA p.Trp240Arg (c.718T>C) pathogenic?

COPA p.Trp240Arg (c.718T>C) is classified Pathogenic in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-01). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1.

How common is COPA p.Trp240Arg (c.718T>C) in the general population?

COPA p.Trp240Arg (c.718T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPA p.Trp240Arg (c.718T>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

COPA p.Trp240Arg

c.718T>C · rs1659063174 · VCV1013258

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic ✓ concordant with ClinVar · top 3% in COPA
REVEL	0.654	pathogenic-leaning
SaProt	LLR -14.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	32.0	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.Trp240Arg
Coding: c.718T>C
MANE Select: NM_004371
dbSNP: rs1659063174
Type: single nucleotide variant
Location: chr1:160314114 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 240: a β-strand

Full COPA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
COPA p.Ala469Val Uncertain significance ★★ ⚠ same type
COPA p.Ala510Thr 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-trp240arg (accessed [today's date]).

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