Is PEX6 p.Leu36= (c.108G>C) pathogenic?

PEX6 p.Leu36= (c.108G>C) is classified Likely benign in PEX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-27). Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Leu36= (c.108G>C)?

PEX6 p.Leu36= (c.108G>C) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Leu36= (c.108G>C) in the general population?

PEX6 p.Leu36= (c.108G>C) is absent from gnomAD v4.1 (gnomAD).

PEX6 p.Leu36=

c.108G>C · VCV3727971

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -0.56, phastCons 0.98
Overall
CADD	9.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX6
Protein: p.Leu36=
Coding: c.108G>C
MANE Select: NM_000287
Type: single nucleotide variant
Location: chr6:42979043 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.87

Full PEX6 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

PEX6 p.Leu36_Val37insGlyLeu Uncertain significance ★ same residue
PEX6 p.Leu36Met Uncertain significance ★ ⚠ same residue
PEX6 c.1130+1G>A Likely pathogenic ★★ same condition
PEX6 c.1233+1G>A Likely pathogenic ★★ same condition
PEX6 c.1688+1G>A Pathogenic ★★ same condition
PEX6 c.1689-1G>A Likely pathogenic ★★ same condition
PEX6 c.1885-1G>A Likely pathogenic ★★ same condition
PEX6 c.1962-1G>A 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/pex6-p-leu36 (accessed [today's date]).

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