Is PEX1 p.Val504Ter (c.1508_1509dup) pathogenic?

PEX1 p.Val504Ter (c.15081509dup) is classified Pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-28). Very rare (popmax 0.00271%, afr); Associated with Heimler syndrome 1.

What condition is associated with PEX1 p.Val504Ter (c.1508_1509dup)?

PEX1 p.Val504Ter (c.1508_1509dup) is associated with Heimler syndrome 1 (ClinVar).

How common is PEX1 p.Val504Ter (c.1508_1509dup) in the general population?

PEX1 p.Val504Ter (c.1508_1509dup) is very rare (popmax 0.00271%, afr) (gnomAD).

PEX1 p.Val504Ter

c.1508_1509dup · rs1489711400 · VCV2677602

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

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 8 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.081	GERP 2.3, phastCons 0.7
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% African / African-American · 2/73,884 alleles

Filtering AF 0.000449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000168%

Overall 0.000128% 2/1,567,256 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.Val504Ter
Coding: c.1508_1509dup
MANE Select: NM_000466
dbSNP: rs1489711400
Type: Microsatellite
Location: chr7:92511021 (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 c.1671_1672del Pathogenic ★★ same condition
PEX1 p.Leu1024fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Val19fs Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Ala311fs Likely pathogenic ★ same condition
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ same condition
PEX1 c.1670+1G>T 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-val504ter (accessed [today's date]).

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