Is COPB2 p.Val83Met (c.247G>A) pathogenic?

COPB2 p.Val83Met (c.247G>A) is classified Likely benign in COPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-03). AlphaMissense: likely pathogenic (0.8574); Rare (popmax 0.38%, eas).

How common is COPB2 p.Val83Met (c.247G>A) in the general population?

COPB2 p.Val83Met (c.247G>A) is rare (popmax 0.38%, eas) (gnomAD).

What do computational predictors say about COPB2 p.Val83Met (c.247G>A)?

AlphaMissense predicts likely pathogenic (score 0.8574) — an in-silico prediction, not a clinical call.

COPB2 p.Val83Met

c.247G>A · rs79043251 · VCV2049493

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8574 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.38%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8574	likely pathogenic
REVEL	0.816	moderately pathogenic-leaning
SaProt	LLR -14.73	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 7.6	GERP 2.5, 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 0.38% East Asian · 170/44,792 alleles

Filtering AF 0.333% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.315%

Overall 0.0217% 347/1,600,640 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.38%	263
Ashkenazi Jewishnot grpmax-eligible	0.173%	577
South Asian	0.0718%	1,393
Remaining individualsnot grpmax-eligible	0.0242%	4,132
European (non-Finnish)	0.00417%	23,999

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.Val83Met
Coding: c.247G>A
MANE Select: NM_004766
dbSNP: rs79043251
Type: single nucleotide variant
Location: chr3:139379155 (GRCh38)
Gene constraint: LOEUF 0.177 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.75 · 2 PDB
Residue 83: a β-strand

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

Similar variants

COPB2 p.Val83fs Pathogenic ★ same residue
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

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-val83met (accessed [today's date]).

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