Is COPB1 p.Arg64His (c.191G>A) pathogenic?

COPB1 p.Arg64His (c.191G>A) is classified Uncertain significance in COPB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.9182); Very rare (popmax 0.00167%, amr).

How common is COPB1 p.Arg64His (c.191G>A) in the general population?

COPB1 p.Arg64His (c.191G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about COPB1 p.Arg64His (c.191G>A)?

AlphaMissense predicts likely pathogenic (score 0.9182) — an in-silico prediction, not a clinical call.

COPB1 p.Arg64His

c.191G>A · rs1324244888 · VCV3076224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9182 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9182	likely pathogenic
REVEL	0.654	pathogenic-leaning
SaProt	LLR -13.02	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,669 bp · p 0.12 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00167% Admixed American · 1/59,998 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,452 alleles · very rare exomes 5/1,461,316 · genomes 0/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
Finnishnot grpmax-eligible	0.00156%	63,974
European (non-Finnish)	0.000254%	393,205

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.Arg64His
Coding: c.191G>A
MANE Select: NM_001144061
dbSNP: rs1324244888
Type: single nucleotide variant
Location: chr11:14494340 (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.Arg64Cys 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-arg64his (accessed [today's date]).

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