Is COPB1 p.Val7Ile (c.19G>A) pathogenic?

COPB1 p.Val7Ile (c.19G>A) is classified Uncertain significance in COPB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.067); Ultra-rare (popmax 0.0689%, mid).

How common is COPB1 p.Val7Ile (c.19G>A) in the general population?

COPB1 p.Val7Ile (c.19G>A) is ultra-rare (popmax 0.0689%, mid) (gnomAD).

What do computational predictors say about COPB1 p.Val7Ile (c.19G>A)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

COPB1 p.Val7Ile

c.19G>A · rs774061544 · VCV2456901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0689%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,669 bp · p 0.12 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0689% Middle Eastern · 4/5,806 alleles

Filtering AF 0.0259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00193% 31/1,608,258 alleles · ultra-rare exomes 24/1,456,856 · genomes 7/151,402 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0689%	1,452
East Asian	0.0402%	2,488
Remaining individualsnot grpmax-eligible	0.00802%	12,464
African / African-American	0.00134%	74,408
European (non-Finnish)	0.000254%	392,941

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.Val7Ile
Coding: c.19G>A
MANE Select: NM_001144061
dbSNP: rs774061544
Type: single nucleotide variant
Location: chr11:14498910 (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.Val7= Likely benign ★ 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-val7ile (accessed [today's date]).

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