Is PEX6 p.Ser942= (c.2826A>G) pathogenic?

PEX6 p.Ser942= (c.2826A>G) is classified Likely benign in PEX6 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-31). Very rare (popmax 0.000254%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Ser942= (c.2826A>G)?

PEX6 p.Ser942= (c.2826A>G) is associated with peroxisome biogenesis disorder, Zellweger spectrum disorders (ClinVar).

How common is PEX6 p.Ser942= (c.2826A>G) in the general population?

PEX6 p.Ser942= (c.2826A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

PEX6 p.Ser942=

c.2826A>G · rs2114235359 · VCV1609168

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 -13	GERP -3.4
Overall
CADD	0.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,854 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,564 alleles · very rare exomes 3/1,461,226 · genomes 0/152,338 · 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.Ser942=
Coding: c.2826A>G
MANE Select: NM_000287
dbSNP: rs2114235359
Type: single nucleotide variant
Location: chr6:42964452 (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

Also linked: Zellweger spectrum disorders

Similar variants

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
PEX6 c.2094+1G>A Likely pathogenic ★★ same condition
PEX6 c.2095-2A>G 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-ser942 (accessed [today's date]).

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