Is COPG2 p.Arg130Ser (c.390G>T) pathogenic?

COPG2 p.Arg130Ser (c.390G>T) is classified Uncertain significance in COPG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: ambiguous (0.3736); Very rare (popmax 8.51e-05%, nfe).

How common is COPG2 p.Arg130Ser (c.390G>T) in the general population?

COPG2 p.Arg130Ser (c.390G>T) is very rare (popmax 8.51e-05%, nfe) (gnomAD).

What do computational predictors say about COPG2 p.Arg130Ser (c.390G>T)?

AlphaMissense predicts ambiguous (score 0.3736) — an in-silico prediction, not a clinical call.

COPG2 p.Arg130Ser

c.390G>T · VCV3268965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.51e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3736	ambiguous
REVEL	0.268	benign-leaning
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP -3.3, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 162 kb · p 0.046 · regional, not allelic
Overall
CADD	18.04	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 8.51e-05% European (non-Finnish) · 1/1,175,726 alleles

Overall 6.87e-05% 1/1,456,300 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: COPG2
Protein: p.Arg130Ser
Coding: c.390G>T
MANE Select: NM_012133
Type: single nucleotide variant
Location: chr7:130616999 (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.Arg32Cys 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-arg130ser (accessed [today's date]).

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