Is PEX1 p.Leu993fs (c.2977dup) pathogenic?

PEX1 p.Leu993fs (c.2977dup) is classified Pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). No gnomAD frequency available for this variant; Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Leu993fs (c.2977dup)?

PEX1 p.Leu993fs (c.2977dup) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Leu993fs (c.2977dup) in the general population?

PEX1 p.Leu993fs (c.2977dup) is no gnomAD frequency available for this variant (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Leu993fs

c.2977dup · rs2116091859 · VCV1415183

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

Zellweger spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 4, 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: PEX1
Protein: p.Leu993fs
Coding: c.2977dup
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs2116091859
Type: Duplication
Location: chr7:92494345 (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-leu993fs (accessed [today's date]).

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