Is PEX1 p.Gln930Ter (c.2788C>T) pathogenic?

PEX1 p.Gln930Ter (c.2788C>T) is classified Pathogenic/Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-13). Very rare (popmax 0.00017%, nfe); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Gln930Ter (c.2788C>T)?

PEX1 p.Gln930Ter (c.2788C>T) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Gln930Ter (c.2788C>T) in the general population?

PEX1 p.Gln930Ter (c.2788C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Gln930Ter

c.2788C>T · rs1791556897 · VCV2769168

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 18 of 24
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 3.8, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,838 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,726 alleles · very rare

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.Gln930Ter
Coding: c.2788C>T
MANE Select: NM_000466
dbSNP: rs1791556897
Type: single nucleotide variant
Location: chr7:92494625 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 930: a UniProt-annotated variant site (in pbd1a)

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

Similar variants

PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ same condition
PEX1 c.1670+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1670+1G>T 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/pex1-p-gln930ter (accessed [today's date]).

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