Is COPA p.Leu43Phe (c.127C>T) pathogenic?

COPA p.Leu43Phe (c.127C>T) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely pathogenic (0.761); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COPA p.Leu43Phe (c.127C>T)?

COPA p.Leu43Phe (c.127C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COPA p.Leu43Phe (c.127C>T) in the general population?

COPA p.Leu43Phe (c.127C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPA p.Leu43Phe (c.127C>T)?

AlphaMissense predicts likely pathogenic (score 0.761) — an in-silico prediction, not a clinical call.

COPA p.Leu43Phe

c.127C>T · VCV3495950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.761 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.761	likely pathogenic
REVEL	0.86	moderately pathogenic-leaning
SaProt	LLR -13.38	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 8.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.48	unconstrained · MANE · 11 kb · p 2.2e-12 · regional, not allelic
Overall
CADD	27.0	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

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.Leu43Phe
Coding: c.127C>T
MANE Select: NM_004371
Type: single nucleotide variant
Location: chr1:160340208 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 43: a β-strand

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-leu43phe (accessed [today's date]).

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