Is CLPB p.Ala13Val (c.38C>T) pathogenic?

CLPB p.Ala13Val (c.38C>T) is classified Uncertain significance in CLPB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely benign (0.0955); Ultra-rare (popmax 0.0108%, amr); Associated with 3-methylglutaconic aciduria, type VIIB.

What condition is associated with CLPB p.Ala13Val (c.38C>T)?

CLPB p.Ala13Val (c.38C>T) is associated with 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Ala13Val (c.38C>T) in the general population?

CLPB p.Ala13Val (c.38C>T) is ultra-rare (popmax 0.0108%, amr) (gnomAD).

What do computational predictors say about CLPB p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

CLPB p.Ala13Val

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.38C>T · rs750927442 · VCV968086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

3-methylglutaconic aciduria, type VIIB

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP -1.6, phastCons 0.94
Regional constraint	o/e 1.01	unconstrained · MANE · 117 kb · p 0.91 · regional, not allelic
Overall
CADD	16.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% Admixed American · 6/55,390 alleles

Filtering AF 0.00468% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00315%

Overall 0.000444% 7/1,577,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0108%	9,232
Finnishnot grpmax-eligible	0.00159%	62,880

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.Ala13Val
Coding: c.38C>T
MANE Select: NM_001258392
dbSNP: rs750927442
Type: single nucleotide variant
Location: chr11:72434437 (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 p.Ala13= Likely benign ★★ same residue
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

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-ala13val (accessed [today's date]).

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