Is CPB2 p.Asn210Ser (c.629A>G) pathogenic?

CPB2 p.Asn210Ser (c.629A>G) is classified Uncertain significance in CPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: likely benign (0.0768); Very rare (popmax 0.00895%, eas).

How common is CPB2 p.Asn210Ser (c.629A>G) in the general population?

CPB2 p.Asn210Ser (c.629A>G) is very rare (popmax 0.00895%, eas) (gnomAD).

What do computational predictors say about CPB2 p.Asn210Ser (c.629A>G)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

CPB2 p.Asn210Ser

c.629A>G · VCV4006138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00895%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -5.5
Regional constraint	o/e 0.83	unconstrained · MANE · 51 kb · p 0.00014 · regional, not allelic
Overall
CADD	0.009	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 0.00895% East Asian · 4/44,686 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.000691% 11/1,592,020 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00895%	11,171
African / African-American	0.00403%	24,783
South Asian	0.00221%	45,299
European (non-Finnish)	0.000172%	580,191

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.Asn210Ser
Coding: c.629A>G
MANE Select: NM_001872
Type: single nucleotide variant
Location: chr13:46067380 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.32 · 10 PDB
Residue 210: 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-asn210ser (accessed [today's date]).

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