Is PEX6 p.Ser504= (c.1512T>C) pathogenic?

PEX6 p.Ser504= (c.1512T>C) is classified Likely benign in PEX6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-16). Very rare (popmax 0.00333%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Ser504= (c.1512T>C)?

PEX6 p.Ser504= (c.1512T>C) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Ser504= (c.1512T>C) in the general population?

PEX6 p.Ser504= (c.1512T>C) is very rare (popmax 0.00333%, nfe) (gnomAD).

PEX6 p.Ser504=

c.1512T>C · rs1013102900 · VCV794382

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, 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 -1.2	GERP -3
Overall
CADD	1.054	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% European (non-Finnish) · 39/1,170,406 alleles

Filtering AF 0.00249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00219%

Overall 0.00251% 40/1,594,458 alleles · very rare exomes 39/1,442,282 · genomes 1/152,176 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00333%	30,010
African / African-American	0.00134%	74,404

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.Ser504=
Coding: c.1512T>C
MANE Select: NM_000287
dbSNP: rs1013102900
Type: single nucleotide variant
Location: chr6:42968466 (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.Ser504Asn 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
PEX6 c.2094+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-ser504 (accessed [today's date]).

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