Is PEX2 p.Gln96= (c.288G>A) pathogenic?

PEX2 p.Gln96= (c.288G>A) is classified Likely benign in PEX2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Ultra-rare (popmax 0.0112%, nfe); Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 p.Gln96= (c.288G>A)?

PEX2 p.Gln96= (c.288G>A) is associated with peroxisome biogenesis disorder 5A (Zellweger), Zellweger spectrum disorders (ClinVar).

How common is PEX2 p.Gln96= (c.288G>A) in the general population?

PEX2 p.Gln96= (c.288G>A) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

PEX2 p.Gln96=

c.288G>A · rs370236723 · VCV765168

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Conditions

peroxisome biogenesis disorder 5A (Zellweger)

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
Constraint at this position
Conservation	phyloP -0.54	GERP -3.8, phastCons 0.02
Overall
CADD	3.675	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0112% European (non-Finnish) · 132/1,180,020 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00849% 137/1,613,988 alleles · ultra-rare exomes 124/1,461,882 · genomes 13/152,106 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,940
Remaining individualsnot grpmax-eligible	0.0032%	31,241
African / African-American	0.00267%	37,448
Admixed American	0.00167%	59,994

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.Gln96=
Coding: c.288G>A
MANE Select: NM_000318
dbSNP: rs370236723
Type: single nucleotide variant
Location: chr8:76983891 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 96: a UniProt-annotated variant site (in pbd5a)

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

Disease context

peroxisome biogenesis disorder 5A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Zellweger spectrum disorders

Similar variants

PEX2 p.Gln96Ter Pathogenic ★★ same residue
PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Arg119Ter Pathogenic ★★ same condition
PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln31Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln78Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Glu168Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Glu53Ter 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-gln96 (accessed [today's date]).

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