Is COPA p.Gly166Val (c.497G>T) pathogenic?

COPA p.Gly166Val (c.497G>T) is classified Uncertain significance in COPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-17). AlphaMissense: ambiguous (0.4783); Very rare (popmax 0.000679%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COPA p.Gly166Val (c.497G>T)?

COPA p.Gly166Val (c.497G>T) is associated with Inborn genetic diseases (ClinVar).

How common is COPA p.Gly166Val (c.497G>T) in the general population?

COPA p.Gly166Val (c.497G>T) is very rare (popmax 0.000679%, nfe) (gnomAD).

What do computational predictors say about COPA p.Gly166Val (c.497G>T)?

AlphaMissense predicts ambiguous (score 0.4783) — an in-silico prediction, not a clinical call.

COPA p.Gly166Val

c.497G>T · rs1424434292 · VCV3076214

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4783 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000679%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4783	ambiguous
REVEL	0.577	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	Δ0.34	acceptor loss · deltas
Pangolin	Δ0.30	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 42 kb · p 1.1e-24 · regional, not allelic
Overall
CADD	29.2	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 0.000679% European (non-Finnish) · 8/1,178,078 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,611,718 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.Gly166Val
Coding: c.497G>T
MANE Select: NM_004371
dbSNP: rs1424434292
Type: single nucleotide variant
Location: chr1:160325652 (GRCh38)
Gene constraint: LOEUF 0.098 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.85 · 3 PDB
Residue 166: an α-helix

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-gly166val (accessed [today's date]).

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