Is PEX2 p.Leu151Val (c.451C>G) pathogenic?

PEX2 p.Leu151Val (c.451C>G) is classified Uncertain significance in PEX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.1116); Absent from gnomAD v4.1; Associated with Zellweger spectrum disorders.

What condition is associated with PEX2 p.Leu151Val (c.451C>G)?

PEX2 p.Leu151Val (c.451C>G) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX2 p.Leu151Val (c.451C>G) in the general population?

PEX2 p.Leu151Val (c.451C>G) is absent from gnomAD v4.1 (gnomAD).

How is Zellweger syndrome inherited?

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

What do computational predictors say about PEX2 p.Leu151Val (c.451C>G)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

PEX2 p.Leu151Val

c.451C>G · VCV4059617

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.572	indeterminate
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.42	GERP -4.9, phastCons 0.001
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic
Overall
CADD	5.561	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX2
Protein: p.Leu151Val
Coding: c.451C>G
MANE Select: NM_000318
Type: single nucleotide variant
Location: chr8:76983728 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 151: a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and pbd5a)

Full PEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Zellweger spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Zellweger syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PEX2 p.Leu151Pro Uncertain significance ★ ⚠ same residue
PEX2 p.Leu151= Likely benign ★ same residue
PEX2 p.Arg119Ter Pathogenic ★★ same condition
PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln31Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Trp105Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Ala8Val Uncertain significance ★★ ⚠ same condition
PEX2 p.Arg125Gln 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/pex2-p-leu151val (accessed [today's date]).

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