Is PEX5 p.Ala548= (c.1644C>T) pathogenic?

PEX5 p.Ala548= (c.1644C>T) is classified Likely benign in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). Very rare (popmax 0.00407%, afr); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Ala548= (c.1644C>T)?

PEX5 p.Ala548= (c.1644C>T) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Ala548= (c.1644C>T) in the general population?

PEX5 p.Ala548= (c.1644C>T) is very rare (popmax 0.00407%, afr) (gnomAD).

PEX5 p.Ala548=

c.1644C>T · rs920189030 · VCV1530589

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00407%, 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 -0.01	GERP -3, phastCons 0.75
Overall
CADD	9.736	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% African / African-American · 3/73,780 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000499%

Overall 0.000248% 4/1,610,560 alleles · very rare exomes 2/1,461,872 · genomes 2/148,688 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00407%	24,593
East Asian	0.00223%	44,744

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.Ala548=
Coding: c.1644C>T
MANE Select: NM_001351132
dbSNP: rs920189030
Type: single nucleotide variant
Location: chr12:7209766 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 548: a UniProt-annotated variant site (in pbd2b; impaired ability to mediate peroxisomal import of proteins containing both a c-terminal pts1- and pts2-type targeting signals); 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 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-ala548 (accessed [today's date]).

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