Is COPB2 p.Ser15= (c.45T>G) pathogenic?

COPB2 p.Ser15= (c.45T>G) is classified Likely benign in COPB2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-19). Very rare (popmax 0.00181%, amr); Associated with COPB2-related disorder.

What condition is associated with COPB2 p.Ser15= (c.45T>G)?

COPB2 p.Ser15= (c.45T>G) is associated with COPB2-related disorder (ClinVar).

How common is COPB2 p.Ser15= (c.45T>G) in the general population?

COPB2 p.Ser15= (c.45T>G) is very rare (popmax 0.00181%, amr) (gnomAD).

COPB2 p.Ser15=

c.45T>G · rs774396539 · VCV3050004

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00181%, amr)

Conditions

COPB2-related disorder

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 -3.9	GERP -4.6
Overall
CADD	3.741	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00181% Admixed American · 1/55,102 alleles

Filtering AF 0.000249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00016%

Overall 0.000566% 9/1,589,696 alleles · very rare exomes 8/1,437,510 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00181%	55,102
African / African-American	0.00135%	74,100
European (non-Finnish)	0.000599%	167,058

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.Ser15=
Coding: c.45T>G
MANE Select: NM_004766
dbSNP: rs774396539
Type: single nucleotide variant
Location: chr3:139383394 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.75 · 2 PDB

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

Disease context

COPB2-related disorder

Similar variants

COPB2 p.Gln356Ter Uncertain significance same condition
COPB2 p.Lys413fs Uncertain significance ★ same condition
COPB2 p.Thr636fs Uncertain significance ★ same condition
COPB2 c.229-10_229-9del Likely benign same condition
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

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-ser15 (accessed [today's date]).

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