Is CLPB p.Arg387Ter (c.1159C>T) pathogenic?

CLPB p.Arg387Ter (c.1159C>T) is classified Pathogenic in CLPB (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-04). Ultra-rare (popmax 0.0108%, nfe); Associated with CLPB-related disorder.

What condition is associated with CLPB p.Arg387Ter (c.1159C>T)?

CLPB p.Arg387Ter (c.1159C>T) is associated with CLPB-related disorder, premature menopause, neutropenia (ClinVar).

How common is CLPB p.Arg387Ter (c.1159C>T) in the general population?

CLPB p.Arg387Ter (c.1159C>T) is ultra-rare (popmax 0.0108%, nfe) (gnomAD).

CLPB p.Arg387Ter

c.1159C>T · rs200203460 · VCV187786

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Conditions

CLPB-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0108% European (non-Finnish) · 127/1,179,938 alleles

Filtering AF 0.00919% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00863%

Overall 0.00882% 129/1,461,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,291
Remaining individualsnot grpmax-eligible	0.0016%	62,508
African / African-American	0.00133%	75,008

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.Arg387Ter
Coding: c.1159C>T
MANE Select: NM_001258392
dbSNP: rs200203460
Type: single nucleotide variant
Location: chr11:72302312 (GRCh38)
Gene constraint: LOEUF 0.643 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.52 · 7 PDB
Residue 387: a binding site; an α-helix

Full CLPB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CLPB-related disorder

Also linked: premature menopause neutropenia 3-methylglutaconic aciduria, type VIIB neutropenia, severe congenital, 9, autosomal dominant 3-methylglutaconic aciduria, type VIIA

Similar variants

CLPB p.Arg387Gln Uncertain significance ★ ⚠ 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-arg387ter (accessed [today's date]).

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