Is PEX2 p.Asp275= (c.825C>T) pathogenic?

PEX2 p.Asp275= (c.825C>T) is classified Conflicting classifications of pathogenicity in PEX2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-22). Ultra-rare (popmax 0.0329%, mid); Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 p.Asp275= (c.825C>T)?

PEX2 p.Asp275= (c.825C>T) is associated with peroxisome biogenesis disorder 5A (Zellweger), Zellweger spectrum disorders (ClinVar).

How common is PEX2 p.Asp275= (c.825C>T) in the general population?

PEX2 p.Asp275= (c.825C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

PEX2 p.Asp275=

c.825C>T · rs367649632 · VCV497960

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, 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 0.46	GERP -3.7, phastCons 0.04
Overall
CADD	10.46	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00192% 31/1,613,810 alleles · ultra-rare exomes 30/1,461,712 · genomes 1/152,098 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.008%	12,497
East Asian	0.00223%	44,888
South Asian	0.0022%	45,541
European (non-Finnish)	0.00169%	58,999
Admixed American	0.00167%	59,992

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.Asp275=
Coding: c.825C>T
MANE Select: NM_000318
dbSNP: rs367649632
Type: single nucleotide variant
Location: chr8:76983354 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 275: 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

Also linked: Zellweger spectrum disorders

Similar variants

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
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-asp275 (accessed [today's date]).

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