Is COPB2 p.Ile243Val (c.727A>G) pathogenic?

COPB2 p.Ile243Val (c.727A>G) is classified Likely benign in COPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely benign (0.0731); Ultra-rare (popmax 0.0669%, eas); Associated with Inborn genetic diseases.

What condition is associated with COPB2 p.Ile243Val (c.727A>G)?

COPB2 p.Ile243Val (c.727A>G) is associated with Inborn genetic diseases (ClinVar).

How common is COPB2 p.Ile243Val (c.727A>G) in the general population?

COPB2 p.Ile243Val (c.727A>G) is ultra-rare (popmax 0.0669%, eas) (gnomAD).

What do computational predictors say about COPB2 p.Ile243Val (c.727A>G)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

COPB2 p.Ile243Val

c.727A>G · VCV4616384

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 28 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	22.7	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 0.0669% East Asian · 30/44,874 alleles

Filtering AF 0.0481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.00551% 89/1,613,894 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0669%	1,496
Middle Eastern	0.0329%	3,040
Finnishnot grpmax-eligible	0.0328%	3,049
African / African-American	0.004%	24,975
Admixed American	0.00333%	30,000
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00246%	40,687

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.Ile243Val
Coding: c.727A>G
MANE Select: NM_004766
Type: single nucleotide variant
Location: chr3:139374513 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.75 · 2 PDB
Residue 243: 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-ile243val (accessed [today's date]).

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