Is PEX26 p.Pro33Arg (c.98C>G) pathogenic?

PEX26 p.Pro33Arg (c.98C>G) is classified Uncertain significance in PEX26 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). AlphaMissense: likely benign (0.0939); No allele count reported in gnomAD v4.1 (AN 1,573,430); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Pro33Arg (c.98C>G)?

PEX26 p.Pro33Arg (c.98C>G) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Pro33Arg (c.98C>G) in the general population?

PEX26 p.Pro33Arg (c.98C>G) is no allele count reported in gnomAD v4.1 (AN 1,573,430) (gnomAD).

What do computational predictors say about PEX26 p.Pro33Arg (c.98C>G)?

AlphaMissense predicts likely benign (score 0.0939) — an in-silico prediction, not a clinical call.

PEX26 p.Pro33Arg

c.98C>G · rs368118099 · VCV1372403

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0939 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,573,430)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

peroxisome biogenesis disorder 7A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.0939	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP 1.4
Regional constraint	o/e 0.98	unconstrained · MANE · 9,695 bp · p 0.72 · regional, not allelic
Overall
CADD	14.27	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,573,430). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX26
Protein: p.Pro33Arg
Coding: c.98C>G
MANE Select: NM_001127649
dbSNP: rs368118099
Type: single nucleotide variant
Location: chr22:18078474 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87

Full PEX26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 7A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 7B

Similar variants

PEX26 p.Pro33Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
PEX26 p.Pro33= Likely benign ★ same residue
PEX26 c.230+1G>T Pathogenic ★★ same condition
PEX26 c.667+2T>C Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Gln146Ter Pathogenic ★★ same condition
PEX26 p.Gly89Arg Pathogenic/Likely 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/pex26-p-pro33arg (accessed [today's date]).

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