Is COPB2 p.Thr357= (c.1071T>G) pathogenic?

COPB2 p.Thr357= (c.1071T>G) is classified Likely benign in COPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). Ultra-rare (popmax 0.0165%, mid).

How common is COPB2 p.Thr357= (c.1071T>G) in the general population?

COPB2 p.Thr357= (c.1071T>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

COPB2 p.Thr357=

c.1071T>G · VCV4781812

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -4.4, phastCons 0.68
Overall
CADD	6.838	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,058 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,766 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
European (non-Finnish)	0.000169%	589,977

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: COPB2
Protein: p.Thr357=
Coding: c.1071T>G
MANE Select: NM_004766
Type: single nucleotide variant
Location: chr3:139373236 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.75 · 2 PDB
Residue 357: a β-strand

Full COPB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPB2 p.Thr357Asn Uncertain significance ★ ⚠ same residue
COPB2 p.Thr357Ser Uncertain significance ★ ⚠ same residue
COPB2 p.Glu646Lys Uncertain significance ★★ ⚠ same type
COPB2 p.Glu879Lys Uncertain significance ★★ ⚠ same type
COPB2 p.Ile864Thr Uncertain significance ★★ ⚠ same type
COPB2 p.Leu649Phe Uncertain significance ★★ ⚠ same type
COPB2 p.Ser135Ala Uncertain significance ★★ ⚠ same type
COPB2 c.1095-23T>C Benign ★★ 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/copb2-p-thr357 (accessed [today's date]).

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