Is CPB2 p.Gln67Arg (c.200A>G) pathogenic?

CPB2 p.Gln67Arg (c.200A>G) is classified Uncertain significance in CPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.0811); Very rare (popmax 0.00891%, eas).

How common is CPB2 p.Gln67Arg (c.200A>G) in the general population?

CPB2 p.Gln67Arg (c.200A>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CPB2 p.Gln67Arg (c.200A>G)?

AlphaMissense predicts likely benign (score 0.0811) — an in-silico prediction, not a clinical call.

CPB2 p.Gln67Arg

c.200A>G · VCV4233219

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0811 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0811	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -4.61	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.2	GERP 0.77, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 51 kb · p 0.00014 · regional, not allelic
Overall
CADD	19.54	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 0.00891% East Asian · 4/44,882 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000274% 4/1,461,856 alleles · very rare

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: CPB2
Protein: p.Gln67Arg
Coding: c.200A>G
Type: single nucleotide variant
Location: chr13:46084294 (GRCh38)

Full CPB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/cpb2-p-gln67arg (accessed [today's date]).

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