Is COPB1 p.Val7= (c.21A>G) pathogenic?

COPB1 p.Val7= (c.21A>G) is classified Likely benign in COPB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Rare (popmax 0.172%, mid).

How common is COPB1 p.Val7= (c.21A>G) in the general population?

COPB1 p.Val7= (c.21A>G) is rare (popmax 0.172%, mid) (gnomAD).

COPB1 p.Val7=

c.21A>G · VCV3770937

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.172%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.093	GERP -4.7, phastCons 0.59
Overall
CADD	9.832	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% Middle Eastern · 10/5,798 alleles

Filtering AF 0.0935% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0712%

Overall 0.0114% 184/1,609,960 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.172%	580
Admixed American	0.0606%	1,649
Remaining individualsnot grpmax-eligible	0.0289%	3,465
European (non-Finnish)	0.0102%	9,826

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: COPB1
Protein: p.Val7=
Coding: c.21A>G
MANE Select: NM_001144061
Type: single nucleotide variant
Location: chr11:14498908 (GRCh38)
Gene constraint: LOEUF 0.269 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.55

Full COPB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COPB1 p.Val7Ile Uncertain significance ★ ⚠ same residue
COPB1 p.Met16Val Uncertain significance ★★ ⚠ same type
COPB1 p.Ser410Arg Uncertain significance ★★ ⚠ same type
COPB1 c.958-4T>G Likely benign ★★ same type
COPB1 p.Leu271= Likely benign ★★ same type
COPB1 p.Phe551Val Pathogenic ★ same type
COPB1 c.1455+2T>C Uncertain significance ★ same type
COPB1 c.1616+2T>C Uncertain significance ★ 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/copb1-p-val7 (accessed [today's date]).

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