Is PEX6 p.Ser184= (c.552C>T) pathogenic?

PEX6 p.Ser184= (c.552C>T) is classified Likely benign in PEX6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-27). Very rare (popmax 0.00167%, amr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Ser184= (c.552C>T)?

PEX6 p.Ser184= (c.552C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Ser184= (c.552C>T) in the general population?

PEX6 p.Ser184= (c.552C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

PEX6 p.Ser184=

c.552C>T · rs1470960597 · VCV2099129

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 0.19	GERP -3.4, phastCons 0.55
Overall
CADD	9.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,882 alleles

Overall 0.000124% 2/1,609,754 alleles · very rare exomes 0/1,457,534 · genomes 2/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,882
European (non-Finnish)	8.48e-05%	1,179,550

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.Ser184=
Coding: c.552C>T
MANE Select: NM_000287
dbSNP: rs1470960597
Type: single nucleotide variant
Location: chr6:42978599 (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 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-ser184 (accessed [today's date]).

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