Is PEX2 p.Arg94fs (c.279_283del) pathogenic?

PEX2 p.Arg94fs (c.279283del) is classified Pathogenic/Likely pathogenic in PEX2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-16). Ultra-rare (popmax 0.0164%, mid); Associated with PEX2-related disorder.

What condition is associated with PEX2 p.Arg94fs (c.279_283del)?

PEX2 p.Arg94fs (c.279_283del) is associated with PEX2-related disorder, peroxisome biogenesis disorder 5A (Zellweger), peroxisome biogenesis disorder 5B (ClinVar).

How common is PEX2 p.Arg94fs (c.279_283del) in the general population?

PEX2 p.Arg94fs (c.279_283del) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PEX2 p.Arg94fs

c.279_283del · rs61752122 · VCV139588

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

PEX2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (4 of 4) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2.4, phastCons 1
Overall
CADD	29.8	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000743% 12/1,614,046 alleles · ultra-rare exomes 10/1,461,880 · genomes 2/152,166 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.000932%	107,275

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: PEX2
Protein: p.Arg94fs
Coding: c.279_283del
MANE Select: NM_000318
dbSNP: rs61752122
Type: Deletion
Location: chr8:76983896 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 94: a UniProt-annotated variant site (in pbd5a)

Full PEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PEX2-related disorder

Also linked: peroxisome biogenesis disorder 5A (Zellweger)peroxisome biogenesis disorder 5B peroxisome biogenesis disorder Zellweger spectrum disorders

Similar variants

PEX2 p.Arg94Gly Uncertain significance ★ ⚠ same residue
PEX2 p.Arg94Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX2 p.Ala58fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Arg119fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Asn12fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Asn73fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Glu118fs Likely pathogenic ★★ same condition
PEX2 p.Gly113_Arg114insTer 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/pex2-p-arg94fs (accessed [today's date]).

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