Is PEX1 p.Glu510Ter (c.1528G>T) pathogenic?

PEX1 p.Glu510Ter (c.1528G>T) is classified Pathogenic/Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-08-05). Very rare (popmax 0.00111%, sas); Associated with Heimler syndrome 1.

What condition is associated with PEX1 p.Glu510Ter (c.1528G>T)?

PEX1 p.Glu510Ter (c.1528G>T) is associated with Heimler syndrome 1, peroxisome biogenesis disorder 1A (Zellweger), peroxisome biogenesis disorder 1B (ClinVar).

How common is PEX1 p.Glu510Ter (c.1528G>T) in the general population?

PEX1 p.Glu510Ter (c.1528G>T) is very rare (popmax 0.00111%, sas) (gnomAD).

PEX1 p.Glu510Ter

c.1528G>T · rs754983126 · VCV371690

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

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 · no allele here is in the release
Pangolin	Δ0.44	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 3.2, phastCons 1
Overall
CADD	38.0	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 0.00111% South Asian · 1/90,062 alleles

Overall 6.97e-05% 1/1,434,934 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.Glu510Ter
Coding: c.1528G>T
MANE Select: NM_000466
dbSNP: rs754983126
Type: single nucleotide variant
Location: chr7:92511003 (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

Also linked: peroxisome biogenesis disorder 1A (Zellweger)peroxisome biogenesis disorder 1B Zellweger spectrum disorders

Similar variants

PEX1 p.Glu510fs Likely pathogenic ★★ same residue
PEX1 p.Glu510Lys Uncertain significance ★ ⚠ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+1G>A 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-glu510ter (accessed [today's date]).

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