Is PEX1 p.Arg626fs (c.1876_1879del) pathogenic?

PEX1 p.Arg626fs (c.18761879del) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-29). Very rare (popmax 0.00134%, afr); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Arg626fs (c.1876_1879del)?

PEX1 p.Arg626fs (c.1876_1879del) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Arg626fs (c.1876_1879del) in the general population?

PEX1 p.Arg626fs (c.1876_1879del) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Arg626fs

c.1876_1879del · VCV4818388

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 11	GERP 3.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,744 alleles

Overall 6.89e-05% 1/1,450,892 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.Arg626fs
Coding: c.1876_1879del
MANE Select: NM_000466
Type: Microsatellite
Location: chr7:92506269 (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.Arg626Thr Uncertain significance ★ ⚠ same residue
PEX1 p.Arg626= Likely benign ★ same residue
PEX1 c.1671_1672del Pathogenic ★★ same condition
PEX1 p.Arg798fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Gln1231fs Pathogenic ★★ same condition
PEX1 p.Glu897_Ser898insTer Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.His572fs Pathogenic ★★ same condition
PEX1 p.His678fs 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-arg626fs (accessed [today's date]).

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