Is PEX1 p.Ser1230Ter (c.3687dup) pathogenic?

PEX1 p.Ser1230Ter (c.3687dup) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). Very rare (popmax 0.0011%, sas); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Ser1230Ter (c.3687dup)?

PEX1 p.Ser1230Ter (c.3687dup) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Ser1230Ter (c.3687dup) in the general population?

PEX1 p.Ser1230Ter (c.3687dup) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Ser1230Ter

c.3687dup · VCV4818408

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 23 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 4, phastCons 0.94

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,024 alleles

Overall 6.85e-05% 1/1,459,202 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PEX1
Protein: p.Ser1230Ter
Coding: c.3687dup
MANE Select: NM_000466
Type: Duplication
Location: chr7:92489372 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 1230: a UniProt-annotated variant site (in pbd1a)

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.Ala668fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.His951fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Ile700fs Pathogenic ★★ same condition
PEX1 p.Ile851fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Leu1177fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Leu826fs Pathogenic ★★ same condition
PEX1 p.Lys614fs Pathogenic ★★ same condition
PEX1 p.Pro934fs 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-ser1230ter (accessed [today's date]).

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