Is PEX1 p.Val723fs (c.2164del) pathogenic?

PEX1 p.Val723fs (c.2164del) is classified Pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Very rare (popmax 0.0011%, sas); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Val723fs (c.2164del)?

PEX1 p.Val723fs (c.2164del) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Val723fs (c.2164del) in the general population?

PEX1 p.Val723fs (c.2164del) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Zellweger syndrome inherited?

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

PEX1 p.Val723fs

c.2164del · rs1792013807 · VCV1404596

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 4.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,074 alleles

Overall 6.84e-05% 1/1,461,506 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.Val723fs
Coding: c.2164del
MANE Select: NM_000466
dbSNP: rs1792013807
Type: Deletion
Location: chr7:92503103 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 723: 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.2072-42_2085del Likely pathogenic ★★ same condition
PEX1 p.Ala15fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Ala921fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg1208fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg827fs Pathogenic ★★ same condition
PEX1 p.Asn1088fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Asn403fs Pathogenic ★★ same condition
PEX1 p.Asp378fs 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/pex1-p-val723fs (accessed [today's date]).

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