Is PEX7 p.Leu32= (c.94C>T) pathogenic?

PEX7 p.Leu32= (c.94C>T) is classified Conflicting classifications of pathogenicity in PEX7 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.526%, eas); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Leu32= (c.94C>T)?

PEX7 p.Leu32= (c.94C>T) is associated with peroxisome biogenesis disorder 9B, rhizomelic chondrodysplasia punctata type 1, rhizomelic chondrodysplasia punctata (ClinVar).

How common is PEX7 p.Leu32= (c.94C>T) in the general population?

PEX7 p.Leu32= (c.94C>T) is rare (popmax 0.526%, eas) (gnomAD).

PEX7 p.Leu32=

c.94C>T · rs886061118 · VCV355526

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.526%, eas)

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP 1.6, phastCons 0.94
Overall
CADD	12.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.526% East Asian · 182/34,620 alleles

Filtering AF 0.463% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.439%

Overall 0.0134% 197/1,474,822 alleles · rare exomes 164/1,322,710 · genomes 33/152,112 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.526%	190
Remaining individualsnot grpmax-eligible	0.0194%	5,162
South Asian	0.00385%	25,993
European (non-Finnish)	8.93e-05%	1,119,731

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: PEX7
Protein: p.Leu32=
Coding: c.94C>T
MANE Select: NM_000288
dbSNP: rs886061118
Type: single nucleotide variant
Location: chr6:136822759 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.54

Full PEX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 9B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhizomelic chondrodysplasia punctata type 1 rhizomelic chondrodysplasia punctata

Similar variants

PEX7 p.Leu32Val Uncertain significance ★ ⚠ same residue
PEX7 c.130+1G>A Pathogenic ★★ same condition
PEX7 c.131-1G>A Likely pathogenic ★★ same condition
PEX7 c.188+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.188+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.340-1G>T Likely pathogenic ★★ same condition
PEX7 c.634-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.748-2A>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/pex7-p-leu32 (accessed [today's date]).

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