Is PEX1 p.Ser1066= (c.3198T>C) pathogenic?

PEX1 p.Ser1066= (c.3198T>C) is classified Conflicting classifications of pathogenicity in PEX1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.028%, afr); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Ser1066= (c.3198T>C)?

PEX1 p.Ser1066= (c.3198T>C) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Ser1066= (c.3198T>C) in the general population?

PEX1 p.Ser1066= (c.3198T>C) is ultra-rare (popmax 0.028%, afr) (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Ser1066=

c.3198T>C · rs150190899 · VCV499941

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.9	GERP -1.6
Overall
CADD	2.705	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/75,010 alleles

Filtering AF 0.0187% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00248% 40/1,613,166 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,572
Middle Eastern	0.0165%	6,060
Admixed American	0.0117%	8,572
Remaining individualsnot grpmax-eligible	0.0048%	20,819
South Asian	0.0011%	91,064
European (non-Finnish)	0.000594%	168,460

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: PEX1
Protein: p.Ser1066=
Coding: c.3198T>C
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs150190899
Type: single nucleotide variant
Location: chr7:92492962 (GRCh38)

Full PEX1 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

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/pex1-p-ser1066 (accessed [today's date]).

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