Is PEX3 p.Gln55= (c.165A>G) pathogenic?

PEX3 p.Gln55= (c.165A>G) is classified Conflicting classifications of pathogenicity in PEX3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.172%, amr); Associated with peroxisome biogenesis disorder 10A (Zellweger).

What condition is associated with PEX3 p.Gln55= (c.165A>G)?

PEX3 p.Gln55= (c.165A>G) is associated with peroxisome biogenesis disorder 10A (Zellweger) (ClinVar).

How common is PEX3 p.Gln55= (c.165A>G) in the general population?

PEX3 p.Gln55= (c.165A>G) is rare (popmax 0.172%, amr) (gnomAD).

PEX3 p.Gln55=

c.165A>G · rs41285015 · VCV195197

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.172%, amr)

Conditions

peroxisome biogenesis disorder 10A (Zellweger)

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 -6.8	GERP -3.6
Overall
CADD	0.524	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.172% Admixed American · 103/60,014 alleles

Filtering AF 0.152% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.129% 2,087/1,612,730 alleles · rare exomes 1,942/1,460,428 · genomes 145/152,302 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.172%	583
European (non-Finnish)	0.158%	632
Remaining individualsnot grpmax-eligible	0.128%	781
African / African-American	0.0267%	3,750
Finnishnot grpmax-eligible	0.0172%	5,820
South Asian	0.00769%	13,007

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: PEX3
Protein: p.Gln55=
Coding: c.165A>G
MANE Select: NM_003630
dbSNP: rs41285015
Type: single nucleotide variant
Location: chr6:143459176 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 55: an α-helix

Full PEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 10A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX3 p.Gln55Pro Uncertain significance ★ ⚠ same residue
PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX3 c.-96G>T Uncertain significance ★★ same condition
PEX3 p.Arg300Gln Uncertain significance ★★ ⚠ same condition
PEX3 p.Asp305Glu Uncertain significance ★★ ⚠ same condition
PEX3 p.Glu266Asp Uncertain significance ★★ ⚠ same condition
PEX3 p.Met270Ile Uncertain significance ★★ ⚠ same condition
PEX3 c.524-19T>C Benign ★★ 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/pex3-p-gln55 (accessed [today's date]).

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