Is PEX1 p.Arg135= (c.403C>A) pathogenic?

PEX1 p.Arg135= (c.403C>A) is classified Likely benign in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-14). Absent from gnomAD v4.1; Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Arg135= (c.403C>A)?

PEX1 p.Arg135= (c.403C>A) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Arg135= (c.403C>A) in the general population?

PEX1 p.Arg135= (c.403C>A) 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.

PEX1 p.Arg135=

c.403C>A · rs201415996 · VCV1666672

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,336)

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.31	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Overall
CADD	11.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,336). 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.Arg135=
Coding: c.403C>A
MANE Select: NM_000466
dbSNP: rs201415996
Type: single nucleotide variant
Location: chr7:92518210 (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.Arg135Ter Pathogenic/Likely pathogenic ★★ same residue
PEX1 p.Arg135Gln Uncertain significance ★ ⚠ same residue
PEX1 p.Arg135fs Likely pathogenic ★ same residue
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
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1483+1G>A 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-arg135 (accessed [today's date]).

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