Is CLPB p.Leu379= (c.1137G>A) pathogenic?

CLPB p.Leu379= (c.1137G>A) is classified Likely benign in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-05). Very rare (popmax 0.00167%, amr); Associated with 3-methylglutaconic aciduria, type VIIB.

What condition is associated with CLPB p.Leu379= (c.1137G>A)?

CLPB p.Leu379= (c.1137G>A) is associated with 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Leu379= (c.1137G>A) in the general population?

CLPB p.Leu379= (c.1137G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

CLPB p.Leu379=

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.1137G>A · rs267603176 · VCV2812245

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 looked up on this page · why
Constraint at this position
Conservation	phyloP -0.51	GERP -3.3, phastCons 0.02
Overall
CADD	13.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,998 alleles

Overall 0.000186% 3/1,614,028 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,998
African / African-American	0.00134%	74,900
European (non-Finnish)	8.47e-05%	1,180,026

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.Leu379=
Coding: c.1137G>A
dbSNP: rs267603176
Type: single nucleotide variant
Location: chr11:72302334 (GRCh38)

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

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-leu379 (accessed [today's date]).

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