Is PEX5 p.Glu61= (c.183G>A) pathogenic?

PEX5 p.Glu61= (c.183G>A) is classified Uncertain significance in PEX5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-16). Very rare (popmax 0.00668%, eas); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Glu61= (c.183G>A)?

PEX5 p.Glu61= (c.183G>A) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Glu61= (c.183G>A) in the general population?

PEX5 p.Glu61= (c.183G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

PEX5 p.Glu61=

c.183G>A · rs767941689 · VCV2010412

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

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	Δ0.49	acceptor loss · deltas
Pangolin	Δ0.64	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 0.18, phastCons 1
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,898 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,612,212 alleles · very rare exomes 3/1,460,048 · genomes 1/152,164 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,966
Remaining individualsnot grpmax-eligible	0.0016%	62,428

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.Glu61=
Coding: c.183G>A
MANE Select: NM_001351132
dbSNP: rs767941689
Type: single nucleotide variant
Location: chr12:7190923 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 61: 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.Glu61Gly 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-glu61 (accessed [today's date]).

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