Is COPA p.Leu706Pro (c.2117T>C) pathogenic?

COPA p.Leu706Pro (c.2117T>C) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely pathogenic (0.9994); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COPA p.Leu706Pro (c.2117T>C)?

COPA p.Leu706Pro (c.2117T>C) is associated with Inborn genetic diseases (ClinVar).

How common is COPA p.Leu706Pro (c.2117T>C) in the general population?

COPA p.Leu706Pro (c.2117T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about COPA p.Leu706Pro (c.2117T>C)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

COPA p.Leu706Pro

c.2117T>C · rs1263191116 · VCV3147971

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 3% in COPA
REVEL	0.947	strongly pathogenic-leaning
SaProt	LLR -16.49	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	28.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,878 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.Leu706Pro
Coding: c.2117T>C
MANE Select: NM_004371
dbSNP: rs1263191116
Type: single nucleotide variant
Location: chr1:160297606 (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.Leu706= Likely benign ★ 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-leu706pro (accessed [today's date]).

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