Is PEX1 p.Ile612fs (c.1833_1834insTT) pathogenic?

PEX1 p.Ile612fs (c.18331834insTT) is classified Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-28). Absent from gnomAD; Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Ile612fs (c.1833_1834insTT)?

PEX1 p.Ile612fs (c.1833_1834insTT) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Ile612fs (c.1833_1834insTT) in the general population?

PEX1 p.Ile612fs (c.1833_1834insTT) is absent from gnomAD (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Ile612fs

c.1833_1834insTT · rs1792185651 · VCV4818386

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	predicted	premature termination codon in exon 11 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.8	GERP -7.6

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.Ile612fs
Coding: c.1833_1834insTT
MANE Select: NM_000466
dbSNP: rs1792185651
Type: Insertion
Location: chr7:92506314 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

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

Similar variants

PEX1 p.Ile612Val Uncertain significance ★ ⚠ same residue
PEX1 c.2584-13_2584-12insG Likely benign ★★ same condition
PEX1 p.Ile482_Ser483insGlu Uncertain significance ★ same condition
PEX1 c.1670+18_1670+19insT Likely benign ★ same condition
PEX1 c.2719-13_2719-12insA Likely benign ★ same condition
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ 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/pex1-p-ile612fs (accessed [today's date]).

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