Is PEX6 p.Thr910= (c.2730G>A) pathogenic?

PEX6 p.Thr910= (c.2730G>A) is classified Likely benign in PEX6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-24). Ultra-rare (popmax 0.0164%, mid); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Thr910= (c.2730G>A)?

PEX6 p.Thr910= (c.2730G>A) is associated with peroxisome biogenesis disorder, peroxisome biogenesis disorder 4A (Zellweger), peroxisome biogenesis disorder 4B (ClinVar).

How common is PEX6 p.Thr910= (c.2730G>A) in the general population?

PEX6 p.Thr910= (c.2730G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PEX6 p.Thr910=

c.2730G>A · rs774721609 · VCV255740

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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 -20	GERP -3.1
Overall
CADD	0.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00816% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00229% 37/1,614,020 alleles · ultra-rare exomes 29/1,461,880 · genomes 8/152,140 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.0147%	6,809
Admixed American	0.0117%	8,571
Remaining individualsnot grpmax-eligible	0.008%	12,496
South Asian	0.00329%	30,363
European (non-Finnish)	0.000847%	118,003

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.Thr910=
Coding: c.2730G>A
MANE Select: NM_000287
dbSNP: rs774721609
Type: single nucleotide variant
Location: chr6:42964866 (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: peroxisome biogenesis disorder 4A (Zellweger)peroxisome biogenesis disorder 4B

Similar variants

PEX6 p.Thr910Met Uncertain significance ★★ ⚠ same residue
PEX6 p.Thr910Ala 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.1961+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-thr910 (accessed [today's date]).

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