Is PEX1 p.Leu1081Pro (c.3242T>C) pathogenic?

PEX1 p.Leu1081Pro (c.3242T>C) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-22). AlphaMissense: likely pathogenic (0.6897); Absent from gnomAD v4.1; Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Leu1081Pro (c.3242T>C)?

PEX1 p.Leu1081Pro (c.3242T>C) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Leu1081Pro (c.3242T>C) in the general population?

PEX1 p.Leu1081Pro (c.3242T>C) 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 PEX1 p.Leu1081Pro (c.3242T>C)?

AlphaMissense predicts likely pathogenic (score 0.6897) — an in-silico prediction, not a clinical call.

PEX1 p.Leu1081Pro

c.3242T>C · rs2116060032 · VCV1511684

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6897 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
AlphaMissense	0.6897	likely pathogenic
REVEL	0.693	pathogenic-leaning
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 3.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

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: PEX1
Protein: p.Leu1081Pro
Coding: c.3242T>C
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs2116060032
Type: single nucleotide variant
Location: chr7:92491468 (GRCh38)

Full PEX1 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

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/pex1-p-leu1081pro (accessed [today's date]).

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