Is PEX2 p.Cys244= (c.732C>T) pathogenic?

PEX2 p.Cys244= (c.732C>T) is classified Likely benign in PEX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Ultra-rare (popmax 0.033%, mid); Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 p.Cys244= (c.732C>T)?

PEX2 p.Cys244= (c.732C>T) is associated with peroxisome biogenesis disorder 5A (Zellweger) (ClinVar).

How common is PEX2 p.Cys244= (c.732C>T) in the general population?

PEX2 p.Cys244= (c.732C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

PEX2 p.Cys244=

c.732C>T · rs142121434 · VCV760152

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 0.52	GERP -4.9, phastCons 0.001
Overall
CADD	5.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,056 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00372% 60/1,614,050 alleles · ultra-rare exomes 55/1,461,768 · genomes 5/152,282 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,028
Remaining individualsnot grpmax-eligible	0.0144%	6,945
South Asian	0.00439%	22,769
European (non-Finnish)	0.00364%	27,442
Admixed American	0.00167%	60,016
Finnishnot grpmax-eligible	0.00156%	63,952

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.Cys244=
Coding: c.732C>T
MANE Select: NM_000318
dbSNP: rs142121434
Type: single nucleotide variant
Location: chr8:76983447 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 244: a binding site; a UniProt-annotated variant site (in pbd5a); a UniProt-annotated variant site (in pbd5b and pbd5a); a UniProt-annotated variant site (in pbd5b)

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.Cys244Ter Likely 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-cys244 (accessed [today's date]).

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