Is PRUNE1 p.Pro161fs (c.476_479dup) pathogenic?

PRUNE1 p.Pro161fs (c.476479dup) is classified Likely pathogenic in PRUNE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-04). Associated with PRUNE1-related disorder.

What condition is associated with PRUNE1 p.Pro161fs (c.476_479dup)?

PRUNE1 p.Pro161fs (c.476_479dup) is associated with PRUNE1-related disorder (ClinVar).

PRUNE1 p.Pro161fs

c.476_479dup · VCV4910484

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

PRUNE1-related disorder

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 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 0.53, phastCons 1

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

Variant & gene context

Gene: PRUNE1
Protein: p.Pro161fs
Coding: c.476_479dup
MANE Select: NM_021222
Type: Duplication
Location: chr1:151024750 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.61

Full PRUNE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PRUNE1-related disorder

Similar variants

PRUNE1 c.521-2A>G Pathogenic/Likely pathogenic ★★ same condition
PRUNE1 p.Asp106Asn Pathogenic/Likely pathogenic ★★ same condition
PRUNE1 p.Thr311= Conflicting classifications of pathogenicity ★ same condition
PRUNE1 p.Arg128Ter Likely pathogenic same condition
PRUNE1 p.Ala160fs Likely pathogenic ★ same type
PRUNE1 p.Asp3fs Pathogenic ★ same type
PRUNE1 p.Glu131fs Pathogenic ★ same type
PRUNE1 p.Leu18fs Pathogenic 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/prune1-p-pro161fs (accessed [today's date]).

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