Is COPA p.Lys8Arg (c.23A>G) pathogenic?

COPA p.Lys8Arg (c.23A>G) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1244); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COPA p.Lys8Arg (c.23A>G)?

COPA p.Lys8Arg (c.23A>G) is associated with Inborn genetic diseases (ClinVar).

How common is COPA p.Lys8Arg (c.23A>G) in the general population?

COPA p.Lys8Arg (c.23A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPA p.Lys8Arg (c.23A>G)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

COPA p.Lys8Arg

c.23A>G · rs2525484260 · VCV3147972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.544	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.7, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 11 kb · p 2.2e-12 · regional, not allelic
Overall
CADD	27.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Lys8Arg
Coding: c.23A>G
MANE Select: NM_004371
dbSNP: rs2525484260
Type: single nucleotide variant
Location: chr1:160343148 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COPA p.Ala422Thr Uncertain significance ★★ ⚠ same condition
COPA p.Arg1009Gln Uncertain significance ★★ ⚠ same condition
COPA p.Arg1142Gln Uncertain significance ★★ ⚠ same condition
COPA p.Arg358Gln Uncertain significance ★★ ⚠ same condition
COPA p.Arg648Leu Uncertain significance ★★ ⚠ same condition
COPA p.Arg745Cys Uncertain significance ★★ ⚠ same condition
COPA p.Arg84Cys Uncertain significance ★★ ⚠ same condition
COPA p.Asp805Gly 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-lys8arg (accessed [today's date]).

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