Is PEX6 p.Thr573= (c.1719A>T) pathogenic?

PEX6 p.Thr573= (c.1719A>T) is classified Likely benign in PEX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-07). Very rare (popmax 0.00017%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Thr573= (c.1719A>T)?

PEX6 p.Thr573= (c.1719A>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Thr573= (c.1719A>T) in the general population?

PEX6 p.Thr573= (c.1719A>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

PEX6 p.Thr573=

c.1719A>T · rs748193406 · VCV1960000

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, 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 -6.4	GERP -3.1
Overall
CADD	0.458	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,834 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,605,714 alleles · very rare exomes 2/1,453,504 · genomes 0/152,210 · 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.Thr573=
Coding: c.1719A>T
MANE Select: NM_000287
dbSNP: rs748193406
Type: single nucleotide variant
Location: chr6:42967533 (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.Thr573Ile Conflicting classifications of pathogenicity ★ ⚠ 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-thr573 (accessed [today's date]).

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