Is PEX6 p.Leu80= (c.238C>T) pathogenic?

PEX6 p.Leu80= (c.238C>T) is classified Likely benign in PEX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). Very rare (popmax 0.000177%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Leu80= (c.238C>T)?

PEX6 p.Leu80= (c.238C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Leu80= (c.238C>T) in the general population?

PEX6 p.Leu80= (c.238C>T) is very rare (popmax 0.000177%, nfe) (gnomAD).

PEX6 p.Leu80=

c.238C>T · VCV3728910

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000177%, nfe)

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.3	GERP 0.5, phastCons 0.99
Overall
CADD	10.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000177% European (non-Finnish) · 2/1,127,798 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000134% 2/1,488,428 alleles · very rare exomes 1/1,336,324 · genomes 1/152,104 · joint denominator

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: PEX6
Protein: p.Leu80=
Coding: c.238C>T
MANE Select: NM_000287
Type: single nucleotide variant
Location: chr6:42978913 (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.Leu80fs Pathogenic/Likely pathogenic ★★ same residue
PEX6 p.Leu80Pro Likely pathogenic ★ ⚠ same residue
PEX6 p.Leu80Val 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

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-leu80 (accessed [today's date]).

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