Is CLPB p.Gly406= (c.1218T>C) pathogenic?

CLPB p.Gly406= (c.1218T>C) is classified Benign/Likely benign in CLPB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-29). Rare (popmax 0.247%, eas); Associated with 3-methylglutaconic aciduria, type VIIB.

What condition is associated with CLPB p.Gly406= (c.1218T>C)?

CLPB p.Gly406= (c.1218T>C) is associated with 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Gly406= (c.1218T>C) in the general population?

CLPB p.Gly406= (c.1218T>C) is rare (popmax 0.247%, eas) (gnomAD).

CLPB p.Gly406=

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.1218T>C · rs200323616 · VCV679616

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.247%, eas)

Conditions

3-methylglutaconic aciduria, type VIIB

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.029	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.51	GERP -0.67, phastCons 0.86
Overall
CADD	7.724	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.247% East Asian · 111/44,870 alleles

Filtering AF 0.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.196%

Overall 0.00706% 114/1,613,980 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.247%	404
Remaining individualsnot grpmax-eligible	0.0048%	20,835

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.Gly406=
Coding: c.1218T>C
dbSNP: rs200323616
Type: single nucleotide variant
Location: chr11:72301914 (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-gly406 (accessed [today's date]).

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