Is COPB2 p.Val83fs (c.247dup) pathogenic?

COPB2 p.Val83fs (c.247dup) is classified Pathogenic in COPB2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-09-08). Absent from gnomAD; Associated with osteoporosis, childhood- or juvenile-onset, with developmental delay.

What condition is associated with COPB2 p.Val83fs (c.247dup)?

COPB2 p.Val83fs (c.247dup) is associated with osteoporosis, childhood- or juvenile-onset, with developmental delay (ClinVar).

How common is COPB2 p.Val83fs (c.247dup) in the general population?

COPB2 p.Val83fs (c.247dup) is absent from gnomAD (gnomAD).

COPB2 p.Val83fs

c.247dup · rs2107807701 · VCV1686976

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

osteoporosis, childhood- or juvenile-onset, with developmental delay

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 4 of 22
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COPB2
Protein: p.Val83fs
Coding: c.247dup
MANE Select: NM_004766
dbSNP: rs2107807701
Type: Duplication
Location: chr3:139379154 (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

Disease context

osteoporosis, childhood- or juvenile-onset, with developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COPB2 p.His556fs Likely pathogenic ★ same condition
COPB2 p.Ser423fs Conflicting classifications of pathogenicity ★ same condition
COPB2 p.Thr636fs Uncertain significance ★ same condition
COPB2 p.Val83Met Likely benign ★ same residue
COPB2 c.1401+2T>A Likely pathogenic ★ same condition
COPB2 p.Glu493fs Likely pathogenic ★ same condition
COPB2 c.751+4A>G Uncertain significance ★ same condition
COPB2 p.Leu439Ser 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-val83fs (accessed [today's date]).

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