Is COPA p.Arg516His (c.1547G>A) pathogenic?

COPA p.Arg516His (c.1547G>A) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely pathogenic (0.7347); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with COPA p.Arg516His (c.1547G>A)?

COPA p.Arg516His (c.1547G>A) is associated with Inborn genetic diseases (ClinVar).

How common is COPA p.Arg516His (c.1547G>A) in the general population?

COPA p.Arg516His (c.1547G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COPA p.Arg516His (c.1547G>A)?

AlphaMissense predicts likely pathogenic (score 0.7347) — an in-silico prediction, not a clinical call.

COPA p.Arg516His

c.1547G>A · rs1431254362 · VCV2403241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7347 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7347	likely pathogenic
REVEL	0.416	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000372% 6/1,613,942 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
African / African-American	0.00134%	74,876
South Asian	0.0011%	91,078
European (non-Finnish)	0.000254%	393,343

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.Arg516His
Coding: c.1547G>A
MANE Select: NM_004371
dbSNP: rs1431254362
Type: single nucleotide variant
Location: chr1:160305553 (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.Arg516Cys Uncertain significance ★ same residue
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

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-arg516his (accessed [today's date]).

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