Is PEX10 p.Pro133Ser (c.397C>T) pathogenic?

PEX10 p.Pro133Ser (c.397C>T) is classified Uncertain significance in PEX10 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-01-13). AlphaMissense: likely benign (0.0733); Absent from gnomAD v4.1; Associated with Zellweger spectrum disorders.

What condition is associated with PEX10 p.Pro133Ser (c.397C>T)?

PEX10 p.Pro133Ser (c.397C>T) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX10 p.Pro133Ser (c.397C>T) in the general population?

PEX10 p.Pro133Ser (c.397C>T) is absent from gnomAD v4.1 (gnomAD).

How is Zellweger syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PEX10 p.Pro133Ser (c.397C>T)?

AlphaMissense predicts likely benign (score 0.0733) — an in-silico prediction, not a clinical call.

PEX10 p.Pro133Ser

c.397C>T · VCV4059608

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0733 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
AlphaMissense	0.0733	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -1.9, phastCons 0.8
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · regional, not allelic
Overall
CADD	2.314	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX10
Protein: p.Pro133Ser
Coding: c.397C>T
MANE Select: NM_002617
Type: single nucleotide variant
Location: chr1:2408655 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81

Full PEX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Zellweger spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Zellweger syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PEX10 p.Pro133= Likely benign ★ same residue
PEX10 c.600+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+2T>C Likely pathogenic ★★ same condition
PEX10 c.777-1G>A Likely pathogenic ★★ same condition
PEX10 c.912+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.913-1G>A Likely pathogenic ★★ same condition
PEX10 p.Arg125Ter 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/pex10-p-pro133ser (accessed [today's date]).

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