Is PEX5 p.Ala157= (c.471C>T) pathogenic?

PEX5 p.Ala157= (c.471C>T) is classified Conflicting classifications of pathogenicity in PEX5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.3%, afr); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Ala157= (c.471C>T)?

PEX5 p.Ala157= (c.471C>T) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Ala157= (c.471C>T) in the general population?

PEX5 p.Ala157= (c.471C>T) is rare (popmax 0.3%, afr) (gnomAD).

PEX5 p.Ala157=

c.471C>T · rs144331955 · VCV167461

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.3%, afr)

Conditions

peroxisome biogenesis disorder 2B

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 1.4	GERP 0.74, phastCons 1
Overall
CADD	10.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.3% African / African-American · 224/74,784 alleles

Filtering AF 0.267% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.255%

Overall 0.0156% 251/1,606,468 alleles · rare exomes 106/1,454,306 · genomes 145/152,162 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.3%	334
Admixed American	0.0285%	3,505
Remaining individualsnot grpmax-eligible	0.0129%	7,769
South Asian	0.00111%	89,938
European (non-Finnish)	8.51e-05%	1,175,458

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.Ala157=
Coding: c.471C>T
MANE Select: NM_001351132
dbSNP: rs144331955
Type: single nucleotide variant
Location: chr12:7199033 (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

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

Similar variants

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
PEX5 p.Arg427Ter 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-ala157 (accessed [today's date]).

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