Is PRUNE1 p.Ala149fs (c.446del) pathogenic?

PRUNE1 p.Ala149fs (c.446del) is classified Pathogenic in PRUNE1 (ClinVar, Single submitter, 1 submitter). Associated with neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies.

PRUNE1 p.Ala149fs

Q: What condition is associated with PRUNE1 p.Ala149fs (c.446del)?

PRUNE1 p.Ala149fs (c.446del) is associated with neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (ClinVar).

c.446del · VCV3382517

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies

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 0.76	GERP -0.55, phastCons 0.064

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

Variant & gene context

Gene: PRUNE1
Protein: p.Ala149fs
Coding: c.446del
MANE Select: NM_021222
Type: Deletion
Location: chr1:151024721 (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

neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRUNE1 c.132+2T>C Pathogenic ★★ same condition
PRUNE1 c.521-2A>G Pathogenic/Likely pathogenic ★★ same condition
PRUNE1 p.Arg128Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
PRUNE1 p.Arg66Ter Pathogenic/Likely pathogenic ★★ same condition
PRUNE1 p.Asp106Asn Pathogenic/Likely pathogenic ★★ same condition
PRUNE1 p.Asp30Asn Pathogenic/Likely pathogenic ★★ same condition
PRUNE1 p.Ala39Pro Uncertain significance ★★ ⚠ same condition
PRUNE1 p.His19Arg Uncertain significance ★★ ⚠ 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/prune1-p-ala149fs (accessed [today's date]).

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