Is PEX3 p.Gln83= (c.249A>G) pathogenic?

PEX3 p.Gln83= (c.249A>G) is classified Conflicting classifications of pathogenicity in PEX3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0223%, nfe); Associated with peroxisome biogenesis disorder 10A (Zellweger).

What condition is associated with PEX3 p.Gln83= (c.249A>G)?

PEX3 p.Gln83= (c.249A>G) is associated with peroxisome biogenesis disorder 10A (Zellweger) (ClinVar).

How common is PEX3 p.Gln83= (c.249A>G) in the general population?

PEX3 p.Gln83= (c.249A>G) is ultra-rare (popmax 0.0223%, nfe) (gnomAD).

PEX3 p.Gln83=

c.249A>G · rs139760270 · VCV355576

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, nfe)

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 -1.2	GERP -3.6
Overall
CADD	1.657	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% European (non-Finnish) · 263/1,179,848 alleles

Filtering AF 0.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0192%

Overall 0.0171% 276/1,613,788 alleles · ultra-rare exomes 261/1,461,634 · genomes 15/152,154 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0223%	4,486
Remaining individualsnot grpmax-eligible	0.016%	6,248
East Asian	0.00223%	44,882
African / African-American	0.00134%	74,886
South Asian	0.0011%	91,084

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.Gln83=
Coding: c.249A>G
MANE Select: NM_003630
dbSNP: rs139760270
Type: single nucleotide variant
Location: chr6:143462959 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 83: 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 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
PEX3 c.942-13A>G 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-gln83 (accessed [today's date]).

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