Is PEX2 c.*1400A>G pathogenic?

PEX2 c.1400A>G is classified Uncertain significance in PEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Ultra-rare (popmax 0.025%, nfe); Associated with peroxisome biogenesis disorder 5A (Zellweger).

What condition is associated with PEX2 c.*1400A>G?

PEX2 c.*1400A>G is associated with peroxisome biogenesis disorder 5A (Zellweger) (ClinVar).

How common is PEX2 c.*1400A>G in the general population?

PEX2 c.*1400A>G is ultra-rare (popmax 0.025%, nfe) (gnomAD).

PEX2 c.*1400A>G

rs1002618013 · VCV910260

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, 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 -0.13	GERP -1.4, phastCons 0.001
Non-coding constraint	Z -1.96	1 kb window · o/e 1.15 · regional · uncalibrated
Overall
CADD	1.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% European (non-Finnish) · 17/68,040 alleles

Filtering AF 0.0159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.0138% 21/152,216 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.025%	4,002
African / African-American	0.00965%	10,362

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
Coding: c.*1400A>G
MANE Select: NM_000318
dbSNP: rs1002618013
Type: single nucleotide variant
Location: chr8:76981861 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17

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 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-c-star-1400a-g (accessed [today's date]).

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