Is PEX6 p.Ile323= (c.969C>T) pathogenic?

PEX6 p.Ile323= (c.969C>T) is classified Benign/Likely benign in PEX6 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-29). Rare (popmax 0.469%, sas); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Ile323= (c.969C>T)?

PEX6 p.Ile323= (c.969C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Ile323= (c.969C>T) in the general population?

PEX6 p.Ile323= (c.969C>T) is rare (popmax 0.469%, sas) (gnomAD).

PEX6 p.Ile323=

c.969C>T · rs143001881 · VCV596379

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.469%, sas)

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 -0.24	GERP -3.4, phastCons 0.013
Overall
CADD	7.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.469% South Asian · 427/91,058 alleles

Filtering AF 0.432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.418%

Overall 0.0286% 462/1,613,508 alleles · rare exomes 425/1,461,262 · genomes 37/152,246 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.469%	213
Middle Eastern	0.0662%	1,511
Remaining individualsnot grpmax-eligible	0.0304%	3,289
East Asian	0.0111%	8,975
Admixed American	0.00333%	30,005
Finnishnot grpmax-eligible	0.00156%	64,024
African / African-American	0.00133%	75,004
European (non-Finnish)	0.000254%	393,165

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.Ile323=
Coding: c.969C>T
MANE Select: NM_000287
dbSNP: rs143001881
Type: single nucleotide variant
Location: chr6:42974952 (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.Ile323Val 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-ile323 (accessed [today's date]).

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