Is CLPB p.Phe349= (c.1047C>T) pathogenic?

CLPB p.Phe349= (c.1047C>T) is classified Likely benign in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). Absent from gnomAD v4.1; Associated with 3-methylglutaconic aciduria, type VIIB.

What condition is associated with CLPB p.Phe349= (c.1047C>T)?

CLPB p.Phe349= (c.1047C>T) is associated with 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Phe349= (c.1047C>T) in the general population?

CLPB p.Phe349= (c.1047C>T) is absent from gnomAD v4.1 (gnomAD).

CLPB p.Phe349=

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.1047C>T · rs2539367529 · VCV2695564

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

3-methylglutaconic aciduria, type VIIB

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.215	benign-leaning
Splicing
SpliceAI	Δ0.20	donor loss, 19 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 6.7	GERP 1.6, phastCons 1
Overall
CADD	10.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLPB
Protein: p.Phe349=
Coding: c.1047C>T
MANE Select: NM_001258392
dbSNP: rs2539367529
Type: single nucleotide variant
Location: chr11:72308546 (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

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 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
CLPB p.Arg178Ter Pathogenic ★★ same condition
CLPB p.Arg312Ter Pathogenic/Likely pathogenic ★★ same condition
CLPB p.Arg378Gly Pathogenic/Likely pathogenic ★★ same condition
CLPB p.Arg387Ter 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-phe349 (accessed [today's date]).

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