Is PEX5 p.Pro151Arg (c.452C>G) pathogenic?

PEX5 p.Pro151Arg (c.452C>G) is classified Uncertain significance in PEX5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-16). AlphaMissense: likely benign (0.1666); Ultra-rare (popmax 0.0854%, eas); Associated with Inborn genetic diseases.

What condition is associated with PEX5 p.Pro151Arg (c.452C>G)?

PEX5 p.Pro151Arg (c.452C>G) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 2B, peroxisome biogenesis disorder 2A (Zellweger) (ClinVar).

How common is PEX5 p.Pro151Arg (c.452C>G) in the general population?

PEX5 p.Pro151Arg (c.452C>G) is ultra-rare (popmax 0.0854%, eas) (gnomAD).

What do computational predictors say about PEX5 p.Pro151Arg (c.452C>G)?

AlphaMissense predicts likely benign (score 0.1666) — an in-silico prediction, not a clinical call.

PEX5 p.Pro151Arg

c.452C>G · rs200720523 · VCV597182

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1666 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0854%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1666	likely benign
REVEL	0.544	indeterminate
SaProt	LLR -7.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0854% East Asian · 38/44,484 alleles

Filtering AF 0.0639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0564%

Overall 0.00346% 55/1,590,782 alleles · ultra-rare exomes 41/1,438,580 · genomes 14/152,202 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0854%	1,171
South Asian	0.0146%	6,851
Remaining individualsnot grpmax-eligible	0.00488%	20,507
European (non-Finnish)	8.6e-05%	1,162,580

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.Pro151Arg
Coding: c.452C>G
MANE Select: NM_001351132
dbSNP: rs200720523
Type: single nucleotide variant
Location: chr12:7199014 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 2B peroxisome biogenesis disorder 2A (Zellweger)

Similar variants

PEX5 p.Pro151Leu Uncertain significance ★ ⚠ same residue
PEX5 p.Pro151Ser 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

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-pro151arg (accessed [today's date]).

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