Is COPB2 p.Asn85Asp (c.253A>G) pathogenic?

COPB2 p.Asn85Asp (c.253A>G) is classified Likely benign in COPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). AlphaMissense: likely pathogenic (0.9762); Absent from gnomAD v4.1.

How common is COPB2 p.Asn85Asp (c.253A>G) in the general population?

COPB2 p.Asn85Asp (c.253A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COPB2 p.Asn85Asp (c.253A>G)?

AlphaMissense predicts likely pathogenic (score 0.9762) — an in-silico prediction, not a clinical call.

COPB2 p.Asn85Asp

c.253A>G · rs2472918697 · VCV2835446

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9762 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9762	likely pathogenic
REVEL	0.529	indeterminate
SaProt	LLR -7.52	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 28 kb · p 2.8e-18 · regional, not allelic
Overall
CADD	26.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COPB2
Protein: p.Asn85Asp
Coding: c.253A>G
MANE Select: NM_004766
dbSNP: rs2472918697
Type: single nucleotide variant
Location: chr3:139379149 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.75 · 2 PDB
Residue 85: a β-strand

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

Similar variants

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
COPB2 c.1401+12C>T Likely benign ★★ same type
COPB2 c.141+20G>T 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-asn85asp (accessed [today's date]).

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