Is COPB2 p.Ile7Ser (c.20T>G) pathogenic?

COPB2 p.Ile7Ser (c.20T>G) is classified Uncertain significance in COPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-03). AlphaMissense: likely pathogenic (0.9712); Very rare (popmax 0.00354%, nfe); Associated with Inborn genetic diseases.

What condition is associated with COPB2 p.Ile7Ser (c.20T>G)?

COPB2 p.Ile7Ser (c.20T>G) is associated with Inborn genetic diseases (ClinVar).

How common is COPB2 p.Ile7Ser (c.20T>G) in the general population?

COPB2 p.Ile7Ser (c.20T>G) is very rare (popmax 0.00354%, nfe) (gnomAD).

What do computational predictors say about COPB2 p.Ile7Ser (c.20T>G)?

AlphaMissense predicts likely pathogenic (score 0.9712) — an in-silico prediction, not a clinical call.

COPB2 p.Ile7Ser

c.20T>G · VCV4616386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00354%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9712	likely pathogenic
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -17.36	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 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 28 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	32.0	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 0.00354% European (non-Finnish) · 41/1,157,948 alleles

Filtering AF 0.00263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00237%

Overall 0.00268% 42/1,565,840 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00354%	28,243
Remaining individualsnot grpmax-eligible	0.00166%	60,392

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.Ile7Ser
Coding: c.20T>G
MANE Select: NM_004766
Type: single nucleotide variant
Location: chr3:139383419 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.75 · 2 PDB
Residue 7: a β-strand

Full COPB2 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

COPB2 p.Glu646Lys Uncertain significance ★★ ⚠ same condition
COPB2 p.Glu879Lys Uncertain significance ★★ ⚠ same condition
COPB2 p.Ile864Thr Uncertain significance ★★ ⚠ same condition
COPB2 p.Leu649Phe Uncertain significance ★★ ⚠ same condition
COPB2 p.Ser135Ala Uncertain significance ★★ ⚠ same condition
COPB2 p.Asn285Ser Benign/Likely benign ★★ ⚠ same condition
COPB2 p.Ala480Thr Uncertain significance ★ ⚠ same condition
COPB2 p.Ala719Thr 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/copb2-p-ile7ser (accessed [today's date]).

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