Is PEX1 p.Pro859fs (c.2576_2578delinsTT) pathogenic?

PEX1 p.Pro859fs (c.25762578delinsTT) is classified Pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). Associated with peroxisome biogenesis disorder.

What condition is associated with PEX1 p.Pro859fs (c.2576_2578delinsTT)?

PEX1 p.Pro859fs (c.2576_2578delinsTT) is associated with peroxisome biogenesis disorder (ClinVar).

PEX1 p.Pro859fs

c.2576_2578delinsTT · VCV3366499

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 15 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 4.1, phastCons 1

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

Variant & gene context

Gene: PEX1
Protein: p.Pro859fs
Coding: c.2576_2578delinsTT
MANE Select: NM_000466
Type: Indel
Location: chr7:92501512 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 859: a UniProt-annotated variant site (in pbd1a)

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.Phe253fs Likely 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 p.Pro859Leu Uncertain significance ★ ⚠ same residue
PEX1 p.Pro859Thr Uncertain significance ★ ⚠ same residue

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-pro859fs (accessed [today's date]).

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