Is CPB2 p.Ser338Thr (c.1013G>C) pathogenic?

CPB2 p.Ser338Thr (c.1013G>C) is classified Uncertain significance in CPB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.0856); Very rare (popmax 0.00368%, nfe).

How common is CPB2 p.Ser338Thr (c.1013G>C) in the general population?

CPB2 p.Ser338Thr (c.1013G>C) is very rare (popmax 0.00368%, nfe) (gnomAD).

What do computational predictors say about CPB2 p.Ser338Thr (c.1013G>C)?

AlphaMissense predicts likely benign (score 0.0856) — an in-silico prediction, not a clinical call.

CPB2 p.Ser338Thr

c.1013G>C · VCV4656030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0856 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00368%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0856	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.7	GERP -0.038, phastCons 0.93
Regional constraint	o/e 0.83	unconstrained · MANE · 51 kb · p 0.00014 · regional, not allelic
Overall
CADD	16.95	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 0.00368% European (non-Finnish) · 43/1,167,396 alleles

Filtering AF 0.00278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00247%

Overall 0.00282% 45/1,596,120 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00368%	27,149
Remaining individualsnot grpmax-eligible	0.00162%	61,802
African / African-American	0.00135%	74,266

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.Ser338Thr
Coding: c.1013G>C
Type: single nucleotide variant
Location: chr13:46055836 (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-ser338thr (accessed [today's date]).

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