Is PEX2 p.Gln159= (c.477G>A) pathogenic?

PEX2 p.Gln159= (c.477G>A) is classified Benign/Likely benign in PEX2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-27). Rare (popmax 0.489%, afr); Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 p.Gln159= (c.477G>A)?

PEX2 p.Gln159= (c.477G>A) is associated with peroxisome biogenesis disorder 5A (Zellweger) (ClinVar).

How common is PEX2 p.Gln159= (c.477G>A) in the general population?

PEX2 p.Gln159= (c.477G>A) is rare (popmax 0.489%, afr) (gnomAD).

PEX2 p.Gln159=

c.477G>A · rs35218706 · VCV291153

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.489%, afr)

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	<0.2	all four deltas below 0.2 · C>G here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.95	GERP -4, phastCons 0.003
Overall
CADD	1.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.489% African / African-American · 367/75,044 alleles

Filtering AF 0.448% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.432%

Overall 0.0264% 426/1,614,092 alleles · rare exomes 188/1,461,790 · genomes 238/152,302 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.489%	204
Admixed American	0.0483%	2,070
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Middle Eastern	0.0165%	6,062
East Asian	0.00223%	44,884
European (non-Finnish)	0.000424%	236,002

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.Gln159=
Coding: c.477G>A
MANE Select: NM_000318
dbSNP: rs35218706
Type: single nucleotide variant
Location: chr8:76983702 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 159: a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and 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

Similar variants

PEX2 p.Gln159Ter 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.Gln96Ter Pathogenic ★★ same condition
PEX2 p.Glu168Ter 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-gln159 (accessed [today's date]).

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