Is COPA p.Val840= (c.2520T>G) pathogenic?

COPA p.Val840= (c.2520T>G) is classified Likely benign in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-22). Very rare (popmax 0.00401%, afr).

How common is COPA p.Val840= (c.2520T>G) in the general population?

COPA p.Val840= (c.2520T>G) is very rare (popmax 0.00401%, afr) (gnomAD).

COPA p.Val840=

c.2520T>G · VCV4918452

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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 0.96	GERP -1.4, phastCons 0.93
Overall
CADD	7.138	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,898 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00197% 3/152,086 alleles · very rare

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.Val840=
Coding: c.2520T>G
MANE Select: NM_004371
Type: single nucleotide variant
Location: chr1:160294814 (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.Val840Ala Conflicting classifications of pathogenicity ★ ⚠ 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
COPA p.Ala469Val 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-val840 (accessed [today's date]).

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