Is CPB2 p.Arg342Cys (c.1024C>T) pathogenic?

CPB2 p.Arg342Cys (c.1024C>T) is classified Uncertain significance in CPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-05). AlphaMissense: likely benign (0.1551); Very rare (popmax 0.0045%, eas).

How common is CPB2 p.Arg342Cys (c.1024C>T) in the general population?

CPB2 p.Arg342Cys (c.1024C>T) is very rare (popmax 0.0045%, eas) (gnomAD).

What do computational predictors say about CPB2 p.Arg342Cys (c.1024C>T)?

AlphaMissense predicts likely benign (score 0.1551) — an in-silico prediction, not a clinical call.

CPB2 p.Arg342Cys

c.1024C>T · VCV4656031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1551 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0045%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1551	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -11.32	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.88, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 51 kb · p 0.00014 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0045% East Asian · 2/44,434 alleles

Filtering AF 0.000746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000432%

Overall 0.00117% 17/1,448,002 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0045%	22,217
Remaining individualsnot grpmax-eligible	0.00323%	30,975
African / African-American	0.00134%	74,430
European (non-Finnish)	0.00103%	97,560

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.Arg342Cys
Coding: c.1024C>T
MANE Select: NM_001872
Type: single nucleotide variant
Location: chr13:46055825 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.32 · 10 PDB
Residue 342: the peptidase m14 domain; an α-helix

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

Similar variants

CPB2 p.Asp142= Benign ★★ same type
CPB2 p.Tyr245= Likely benign ★★ same type
CPB2 p.Ala22Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala246Val Uncertain significance ★ ⚠ same type
CPB2 p.Ala340Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala411Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala74Thr Uncertain significance ★ ⚠ same type
CPB2 p.Ala7Glu 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/cpb2-p-arg342cys (accessed [today's date]).

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