Is PEX1 p.Phe253fs (c.757_758delinsA) pathogenic?

PEX1 p.Phe253fs (c.757758delinsA) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-16). Absent from gnomAD; Associated with peroxisome biogenesis disorder.

What condition is associated with PEX1 p.Phe253fs (c.757_758delinsA)?

PEX1 p.Phe253fs (c.757_758delinsA) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX1 p.Phe253fs (c.757_758delinsA) in the general population?

PEX1 p.Phe253fs (c.757_758delinsA) is absent from gnomAD (gnomAD).

PEX1 p.Phe253fs

c.757_758delinsA · rs2484703483 · VCV1726334

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

peroxisome biogenesis disorder

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 5 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: PEX1
Protein: p.Phe253fs
Coding: c.757_758delinsA
MANE Select: NM_000466
dbSNP: rs2484703483
Type: Indel
Location: chr7:92517757 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX1 p.Leu518fs Likely pathogenic ★ same condition
PEX1 p.Met210fs Likely pathogenic ★ same condition
PEX1 p.Pro859fs Pathogenic ★ same condition
PEX1 p.Ser458fs Likely pathogenic ★ same condition
PEX1 p.Thr171delinsIleTer Likely pathogenic ★ same condition
PEX1 p.Thr785fs Likely pathogenic ★ same condition
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-2A>G 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-phe253fs (accessed [today's date]).

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