Is COPB2 p.Gly435Ser (c.1303G>A) pathogenic?

COPB2 p.Gly435Ser (c.1303G>A) is classified Uncertain significance in COPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-24). AlphaMissense: likely benign (0.3297); Ultra-rare (popmax 0.0275%, sas); Associated with Inborn genetic diseases.

What condition is associated with COPB2 p.Gly435Ser (c.1303G>A)?

COPB2 p.Gly435Ser (c.1303G>A) is associated with Inborn genetic diseases (ClinVar).

How common is COPB2 p.Gly435Ser (c.1303G>A) in the general population?

COPB2 p.Gly435Ser (c.1303G>A) is ultra-rare (popmax 0.0275%, sas) (gnomAD).

What do computational predictors say about COPB2 p.Gly435Ser (c.1303G>A)?

AlphaMissense predicts likely benign (score 0.3297) — an in-silico prediction, not a clinical call.

COPB2 p.Gly435Ser

c.1303G>A · VCV3495964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3297 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3297	likely benign
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -13.83	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 28 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	29.2	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 0.0275% South Asian · 25/90,868 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00285% 46/1,612,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0275%	3,635
Admixed American	0.015%	6,654
African / African-American	0.00802%	12,466
Remaining individualsnot grpmax-eligible	0.0032%	31,223
European (non-Finnish)	0.000339%	294,888

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.Gly435Ser
Coding: c.1303G>A
MANE Select: NM_004766
Type: single nucleotide variant
Location: chr3:139369359 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COPB2 p.Gly435= Likely benign ★ same residue
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

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-gly435ser (accessed [today's date]).

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