Is PEX1 p.Val658fs (c.1964_1970dup) pathogenic?

PEX1 p.Val658fs (c.19641970dup) is classified Likely pathogenic in PEX1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-04-05). Absent from gnomAD; Associated with peroxisome biogenesis disorder 1B.

What condition is associated with PEX1 p.Val658fs (c.1964_1970dup)?

PEX1 p.Val658fs (c.1964_1970dup) is associated with peroxisome biogenesis disorder 1B, peroxisome biogenesis disorder 1A (Zellweger) (ClinVar).

How common is PEX1 p.Val658fs (c.1964_1970dup) in the general population?

PEX1 p.Val658fs (c.1964_1970dup) is absent from gnomAD (gnomAD).

PEX1 p.Val658fs

c.1964_1970dup · rs1057517486 · VCV371723

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

peroxisome biogenesis disorder 1B

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 12 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.84	GERP -3

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.Val658fs
Coding: c.1964_1970dup
MANE Select: NM_000466
dbSNP: rs1057517486
Type: Duplication
Location: chr7:92504832 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 658: a UniProt-annotated variant site (in pbd1a and pbd1b)

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

Disease context

peroxisome biogenesis disorder 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 1A (Zellweger)

Similar variants

PEX1 p.His951fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Ile700fs Pathogenic ★★ same condition
PEX1 p.Leu1177fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Lys614fs Pathogenic ★★ same condition
PEX1 p.Pro934fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Thr181fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Thr643fs Pathogenic ★★ same condition
PEX1 p.Trp653_Met654insThrValTrp 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-val658fs (accessed [today's date]).

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