Is PEX2 p.Pro54Ser (c.159_160delinsAT) pathogenic?

PEX2 p.Pro54Ser (c.159160delinsAT) is classified Uncertain significance in PEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-20). No gnomAD frequency available for this variant; Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 p.Pro54Ser (c.159_160delinsAT)?

PEX2 p.Pro54Ser (c.159_160delinsAT) is associated with peroxisome biogenesis disorder 5A (Zellweger) (ClinVar).

How common is PEX2 p.Pro54Ser (c.159_160delinsAT) in the general population?

PEX2 p.Pro54Ser (c.159_160delinsAT) is no gnomAD frequency available for this variant (gnomAD).

PEX2 p.Pro54Ser

c.159_160delinsAT · rs2487453391 · VCV2050712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: PEX2
Protein: p.Pro54Ser
Coding: c.159_160delinsAT
MANE Select: NM_000318
dbSNP: rs2487453391
Type: Indel
Location: chr8:76984019 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 54: 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

Similar variants

PEX2 p.Pro54= Likely benign ★ same residue
PEX2 p.Tyr277Ter Likely pathogenic ★ same condition
PEX2 p.Cys184Leu Uncertain significance ★ same condition
PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Ala58fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Arg119fs Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Arg119Ter Pathogenic ★★ same condition
PEX2 p.Arg125Ter 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-pro54ser (accessed [today's date]).

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