Is CLPB p.Ala119Ser (c.354_355delinsCT) pathogenic?

CLPB p.Ala119Ser (c.354355delinsCT) is classified Uncertain significance in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-24). Absent from gnomAD; Associated with 3-methylglutaconic aciduria, type VIIB.

What condition is associated with CLPB p.Ala119Ser (c.354_355delinsCT)?

CLPB p.Ala119Ser (c.354_355delinsCT) is associated with 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Ala119Ser (c.354_355delinsCT) in the general population?

CLPB p.Ala119Ser (c.354_355delinsCT) is absent from gnomAD (gnomAD).

CLPB p.Ala119Ser

Q: How is 3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.354_355delinsCT · rs2496012012 · VCV2823908

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

3-methylglutaconic aciduria, type VIIB

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 117 kb · p 0.91 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLPB
Protein: p.Ala119Ser
Coding: c.354_355delinsCT
MANE Select: NM_001258392
dbSNP: rs2496012012
Type: Indel
Location: chr11:72434120 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 7 PDB
Residue 119: the 'autoinhibitory' region

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

Disease context

3-methylglutaconic aciduria, type VIIB — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For 3-methylglutaconic aciduria-neonatal cataract-neurologic involvement-congenital neutropenia syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Neonatal

Similar variants

CLPB p.Ala119Gly Uncertain significance ★★ ⚠ same residue
CLPB p.Ala492Cys Likely benign ★★ same condition
CLPB c.1561-11_1561-10delinsCT Uncertain significance ★ same condition
CLPB p.Ala605Lys Pathogenic same condition
CLPB c.1066+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLPB c.455+1G>A Likely pathogenic ★★ same condition
CLPB c.873+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLPB c.874-2A>G Likely pathogenic ★★ 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-ala119ser (accessed [today's date]).

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