Is CLPB p.Asn146Ser (c.437A>G) pathogenic?

CLPB p.Asn146Ser (c.437A>G) is classified Uncertain significance in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.141); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CLPB p.Asn146Ser (c.437A>G)?

CLPB p.Asn146Ser (c.437A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CLPB p.Asn146Ser (c.437A>G) in the general population?

CLPB p.Asn146Ser (c.437A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CLPB p.Asn146Ser (c.437A>G)?

AlphaMissense predicts likely benign (score 0.141) — an in-silico prediction, not a clinical call.

CLPB p.Asn146Ser

c.437A>G · VCV4615968

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.141 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.141	likely benign
REVEL	0.122	moderately benign-leaning
SaProt	LLR -8.55	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 6.2	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 117 kb · p 0.91 · regional, not allelic
Overall
CADD	22.1	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 0.00223% East Asian · 1/44,868 alleles

Overall 6.84e-05% 1/1,461,166 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: CLPB
Protein: p.Asn146Ser
Coding: c.437A>G
MANE Select: NM_001258392
Type: single nucleotide variant
Location: chr11:72430330 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 7 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CLPB p.Ala120Gly Uncertain significance ★★ ⚠ same condition
CLPB p.Ala232Thr Uncertain significance ★★ ⚠ same condition
CLPB p.Ala85Val Uncertain significance ★★ ⚠ same condition
CLPB p.Arg231His Uncertain significance ★★ ⚠ same condition
CLPB p.Arg599Cys Uncertain significance ★★ ⚠ same condition
CLPB p.Arg620His Uncertain significance ★★ ⚠ same condition
CLPB p.Arg620Leu Uncertain significance ★★ ⚠ same condition
CLPB p.Arg644Cys Uncertain significance ★★ ⚠ same condition

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/clpb-p-asn146ser (accessed [today's date]).

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