Is CPB1 p.Gly343Ser (c.1027G>A) pathogenic?

CPB1 p.Gly343Ser (c.1027G>A) is classified Uncertain significance in CPB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). AlphaMissense: likely benign (0.1403); Ultra-rare (popmax 0.0441%, afr).

How common is CPB1 p.Gly343Ser (c.1027G>A) in the general population?

CPB1 p.Gly343Ser (c.1027G>A) is ultra-rare (popmax 0.0441%, afr) (gnomAD).

What do computational predictors say about CPB1 p.Gly343Ser (c.1027G>A)?

AlphaMissense predicts likely benign (score 0.1403) — an in-silico prediction, not a clinical call.

CPB1 p.Gly343Ser

c.1027G>A · rs147578743 · VCV3076588

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1403 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0441%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1403	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -11.05	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 2.5	GERP 0.093, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 32 kb · p 0.33 · regional, not allelic
Overall
CADD	21.3	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 0.0441% African / African-American · 33/74,878 alleles

Filtering AF 0.0322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0281%

Overall 0.00366% 59/1,613,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0441%	2,269
Middle Eastern	0.0329%	3,040
South Asian	0.0022%	45,535
European (non-Finnish)	0.00178%	56,188
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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: CPB1
Protein: p.Gly343Ser
Coding: c.1027G>A
MANE Select: NM_001871
dbSNP: rs147578743
Type: single nucleotide variant
Location: chr3:148857502 (GRCh38)
Gene constraint: LOEUF 1.167 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.71 · 2 PDB
Residue 343: the peptidase m14 domain

Full CPB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPB1 c.778+6T>C Benign ★★ same type
CPB1 p.Ile394Met Benign ★★ ⚠ same type
CPB1 p.Ala127Thr Uncertain significance ★ ⚠ same type
CPB1 p.Ala133Thr Uncertain significance ★ ⚠ same type
CPB1 p.Ala193Ser Uncertain significance ★ ⚠ same type
CPB1 p.Ala285Ser Uncertain significance ★ ⚠ same type
CPB1 p.Ala358Thr Uncertain significance ★ ⚠ same type
CPB1 p.Ala409Ser 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/cpb1-p-gly343ser (accessed [today's date]).

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