Is COPB1 p.Arg64Cys (c.190C>T) pathogenic?

COPB1 p.Arg64Cys (c.190C>T) is classified Uncertain significance in COPB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-07). AlphaMissense: likely pathogenic (0.9396); Very rare (popmax 0.0028%, nfe).

How common is COPB1 p.Arg64Cys (c.190C>T) in the general population?

COPB1 p.Arg64Cys (c.190C>T) is very rare (popmax 0.0028%, nfe) (gnomAD).

What do computational predictors say about COPB1 p.Arg64Cys (c.190C>T)?

AlphaMissense predicts likely pathogenic (score 0.9396) — an in-silico prediction, not a clinical call.

COPB1 p.Arg64Cys

c.190C>T · rs750155761 · VCV3076223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9396 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0028%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9396	likely pathogenic
REVEL	0.698	pathogenic-leaning
SaProt	LLR -13.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Pangolin	Δ0.26	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 4,669 bp · p 0.12 · regional, not allelic
Overall
CADD	35.0	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 0.0028% European (non-Finnish) · 33/1,179,472 alleles

Filtering AF 0.002% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00176%

Overall 0.00223% 36/1,613,188 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0028%	35,742
Admixed American	0.00167%	59,978
African / African-American	0.00134%	74,832
South Asian	0.0011%	91,066

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.Arg64Cys
Coding: c.190C>T
MANE Select: NM_001144061
dbSNP: rs750155761
Type: single nucleotide variant
Location: chr11:14494341 (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.Arg64His 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-arg64cys (accessed [today's date]).

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