Is COPG2 p.Arg32Cys (c.94C>T) pathogenic?

COPG2 p.Arg32Cys (c.94C>T) is classified Uncertain significance in COPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely pathogenic (0.9573); Very rare (popmax 0.00277%, afr).

How common is COPG2 p.Arg32Cys (c.94C>T) in the general population?

COPG2 p.Arg32Cys (c.94C>T) is very rare (popmax 0.00277%, afr) (gnomAD).

What do computational predictors say about COPG2 p.Arg32Cys (c.94C>T)?

AlphaMissense predicts likely pathogenic (score 0.9573) — an in-silico prediction, not a clinical call.

COPG2 p.Arg32Cys

c.94C>T · VCV4005776

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9573 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00277%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9573	likely pathogenic
REVEL	0.695	pathogenic-leaning
SaProt	LLR -14.09	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 12	GERP 4.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 162 kb · p 0.046 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 0.00277% African / African-American · 2/72,088 alleles

Filtering AF 0.00046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000327%

Overall 0.000783% 12/1,532,698 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00277%	36,044
European (non-Finnish)	0.000887%	112,704

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: COPG2
Protein: p.Arg32Cys
Coding: c.94C>T
MANE Select: NM_012133
Type: single nucleotide variant
Location: chr7:130666926 (GRCh38)
Gene constraint: LOEUF 1.132 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.98

Full COPG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPG2 p.Ala96Thr Uncertain significance ★ ⚠ same type
COPG2 p.Arg130Ser Uncertain significance ★ ⚠ same type
COPG2 p.Arg75Gln Uncertain significance ★ ⚠ same type
COPG2 p.Asn179Ser Uncertain significance ★ ⚠ same type
COPG2 p.Asn189Ser Uncertain significance ★ ⚠ same type
COPG2 p.Asn40Thr Uncertain significance ★ ⚠ same type
COPG2 p.Asp207Asn Uncertain significance ★ ⚠ same type
COPG2 p.Asp81Asn Uncertain significance ★ ⚠ same type

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/copg2-p-arg32cys (accessed [today's date]).

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