Is PEX1 p.Ser241fs (c.721del) pathogenic?

PEX1 p.Ser241fs (c.721del) is classified Pathogenic/Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-07-28). Very rare (popmax 0.00579%, amr); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Ser241fs (c.721del)?

PEX1 p.Ser241fs (c.721del) is associated with Zellweger spectrum disorders, peroxisome biogenesis disorder 1A (Zellweger), peroxisome biogenesis disorder 1B (ClinVar).

How common is PEX1 p.Ser241fs (c.721del) in the general population?

PEX1 p.Ser241fs (c.721del) is very rare (popmax 0.00579%, amr) (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Ser241fs

c.721del · rs894289737 · VCV591770

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00579%, amr)

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 5 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP -0.94
Overall
CADD	18.87	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00579% Admixed American · 3/51,772 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000826%

Overall 0.000447% 7/1,564,532 alleles · very rare exomes 3/1,412,362 · genomes 4/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00579%	17,257
Remaining individualsnot grpmax-eligible	0.00498%	20,081
African / African-American	0.00137%	72,934

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.Ser241fs
Coding: c.721del
MANE Select: NM_000466
dbSNP: rs894289737
Type: Deletion
Location: chr7:92517794 (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

Also linked: peroxisome biogenesis disorder 1A (Zellweger)peroxisome biogenesis disorder 1B

For Zellweger syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PEX1 p.Ser241Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX1 p.Ser241= Likely benign ★ same residue
PEX1 c.2072-42_2085del Likely pathogenic ★★ same condition
PEX1 p.Ala15fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Ala921fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg1208fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg827fs Pathogenic ★★ same condition
PEX1 p.Asn1088fs 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-ser241fs (accessed [today's date]).

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