Is CLPB p.Pro94fs (c.278dup) pathogenic?

CLPB p.Pro94fs (c.278dup) is classified Pathogenic in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). Absent from gnomAD; Associated with 3-methylglutaconic aciduria, type VIIB.

What condition is associated with CLPB p.Pro94fs (c.278dup)?

CLPB p.Pro94fs (c.278dup) is associated with 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Pro94fs (c.278dup) in the general population?

CLPB p.Pro94fs (c.278dup) is absent from gnomAD (gnomAD).

CLPB p.Pro94fs

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.278dup · rs2496013518 · VCV2042071

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.42	GERP -2.9, phastCons 0.008

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Pro94fs
Coding: c.278dup
MANE Select: NM_001258392
dbSNP: rs2496013518
Type: Duplication
Location: chr11:72434196 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 7 PDB
Residue 94: 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.Pro94= Likely benign ★ same residue
CLPB p.Asp432fs Pathogenic/Likely pathogenic ★★ same condition
CLPB p.Gln219fs Pathogenic/Likely pathogenic ★★ same condition
CLPB p.Gly76fs Likely pathogenic ★ same condition
CLPB c.1680+2dup Uncertain significance ★ same condition
CLPB c.404-12dup Benign ★ same condition
CLPB c.1066+1G>A Pathogenic/Likely pathogenic ★★ same condition
CLPB c.455+1G>A 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-pro94fs (accessed [today's date]).

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