Is CLPB p.Asn675fs (c.2023_*4del) pathogenic?

CLPB p.Asn675fs (c.20234del) is classified Uncertain significance in CLPB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CLPB p.Asn675fs (c.2023_*4del)?

CLPB p.Asn675fs (c.2023_*4del) is associated with Inborn genetic diseases, 3-methylglutaconic aciduria, type VIIB (ClinVar).

How common is CLPB p.Asn675fs (c.2023_*4del) in the general population?

CLPB p.Asn675fs (c.2023_*4del) is very rare (popmax 0.00144%, nfe) (gnomAD).

CLPB p.Asn675fs

c.2023_*4del · rs1362604874 · VCV1410637

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (16 of 16) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.47	GERP -3.1, phastCons 0.01
Overall
CADD	14.88	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 0.00144% European (non-Finnish) · 17/1,178,190 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000719%

Overall 0.00105% 17/1,611,760 alleles · very rare

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.Asn675fs
Coding: c.2023_*4del
MANE Select: NM_001258392
dbSNP: rs1362604874
Type: Deletion
Location: chr11:72293363 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: 3-methylglutaconic aciduria, type VIIB

Similar variants

CLPB p.Asn675Ser Likely benign ★ same residue
CLPB c.1561-18_1561-12del Likely benign ★★ same condition
CLPB c.403+7_403+8del Likely benign ★★ same condition
CLPB c.543-20_543-18del Likely benign ★★ same condition
CLPB c.1560+2_1560+5del Likely pathogenic ★ same condition
CLPB p.Asp448fs Pathogenic ★ same condition
CLPB p.Leu263fs Pathogenic ★ same condition
CLPB p.Val107fs 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-asn675fs (accessed [today's date]).

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