Is CLPP p.Asp134fs (c.383_399dup) pathogenic?

CLPP p.Asp134fs (c.383399dup) is classified Pathogenic in CLPP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-19). Absent from gnomAD; Associated with Perrault syndrome 1.

What condition is associated with CLPP p.Asp134fs (c.383_399dup)?

CLPP p.Asp134fs (c.383_399dup) is associated with Perrault syndrome 1 (ClinVar).

How common is CLPP p.Asp134fs (c.383_399dup) in the general population?

CLPP p.Asp134fs (c.383_399dup) is absent from gnomAD (gnomAD).

How is Perrault syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CLPP p.Asp134fs

c.383_399dup · rs2512444496 · VCV2579749

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Perrault syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -4.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLPP
Protein: p.Asp134fs
Coding: c.383_399dup
MANE Select: NM_006012
dbSNP: rs2512444496
Type: Duplication
Location: chr19:6364466 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.68 · 32 PDB
Residue 134: an α-helix

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

Disease context

Perrault syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Perrault syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

CLPP p.Asp134His Likely pathogenic ★ same residue
CLPP c.199-31dup Benign ★★ same type
CLPP p.Val12fs Pathogenic ★ same type
CLPP c.555+107dup Likely benign ★ same type
CLPP c.556-295dup Benign ★ same type

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/clpp-p-asp134fs (accessed [today's date]).

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