Is PEX5 p.Arg394= (c.1182G>A) pathogenic?

PEX5 p.Arg394= (c.1182G>A) is classified Uncertain significance in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). Very rare (popmax 0.00272%, nfe); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Arg394= (c.1182G>A)?

PEX5 p.Arg394= (c.1182G>A) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Arg394= (c.1182G>A) in the general population?

PEX5 p.Arg394= (c.1182G>A) is very rare (popmax 0.00272%, nfe) (gnomAD).

PEX5 p.Arg394=

c.1182G>A · rs199624284 · VCV1052375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00272%, nfe)

Conditions

peroxisome biogenesis disorder 2B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.26	acceptor gain · deltas
Pangolin	Δ0.27	gain · loss 0.13 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.8	GERP -0.26, phastCons 1
Overall
CADD	19.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00272% European (non-Finnish) · 32/1,177,858 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00199% 32/1,611,618 alleles · very rare exomes 30/1,459,422 · genomes 2/152,196 · joint denominator

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: PEX5
Protein: p.Arg394=
Coding: c.1182G>A
MANE Select: NM_001351132
dbSNP: rs199624284
Type: single nucleotide variant
Location: chr12:7208457 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 394: an α-helix

Full PEX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX5 p.Arg394Ser Uncertain significance ★ ⚠ same residue
PEX5 c.449-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.552-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.847-2A>G Likely pathogenic ★★ same condition
PEX5 c.967-1G>A Likely pathogenic ★★ same condition
PEX5 p.Arg237Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg420Ter 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/pex5-p-arg394 (accessed [today's date]).

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