Is PEX1 p.Trp246Ter (c.735_737dup) pathogenic?

PEX1 p.Trp246Ter (c.735737dup) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). Absent from gnomAD; Associated with Heimler syndrome 1.

What condition is associated with PEX1 p.Trp246Ter (c.735_737dup)?

PEX1 p.Trp246Ter (c.735_737dup) is associated with Heimler syndrome 1 (ClinVar).

How common is PEX1 p.Trp246Ter (c.735_737dup) in the general population?

PEX1 p.Trp246Ter (c.735_737dup) is absent from gnomAD (gnomAD).

PEX1 p.Trp246Ter

c.735_737dup · rs2484703527 · VCV2677612

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Heimler syndrome 1

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 5 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	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.Trp246Ter
Coding: c.735_737dup
MANE Select: NM_000466
dbSNP: rs2484703527
Type: Duplication
Location: chr7:92517777 (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

Heimler syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX1 p.Ala668fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Leu1177fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Pro934fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Thr643fs Pathogenic ★★ same condition
PEX1 p.Asn830fs Likely pathogenic ★ same condition
PEX1 p.Leu480fs Pathogenic ★ same condition
PEX1 p.Leu865fs Likely pathogenic ★ same condition
PEX1 p.Met248fs 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-trp246ter (accessed [today's date]).

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