Is PEX10 p.Pro3fs (c.8del) pathogenic?

PEX10 p.Pro3fs (c.8del) is classified Pathogenic/Likely pathogenic in PEX10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-08). Ultra-rare (popmax 0.0267%, mid); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Pro3fs (c.8del)?

PEX10 p.Pro3fs (c.8del) is associated with Peroxisome biogenesis disorder, complementation group 7, peroxisome biogenesis disorder 6A (Zellweger) (ClinVar).

How common is PEX10 p.Pro3fs (c.8del) in the general population?

PEX10 p.Pro3fs (c.8del) is ultra-rare (popmax 0.0267%, mid) (gnomAD).

PEX10 p.Pro3fs

c.8del · rs1257198952 · VCV2677655

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, mid)

Conditions

Peroxisome biogenesis disorder, complementation group 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.4	GERP -4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Middle Eastern · 1/3,748 alleles

Filtering AF 8.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.9e-05%

Overall 0.000511% 7/1,370,122 alleles · ultra-rare exomes 7/1,218,022 · genomes 0/152,100 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0267%	3,748
Admixed American	0.00335%	29,864
Remaining individualsnot grpmax-eligible	0.00193%	51,802
European (non-Finnish)	0.000376%	265,936

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: PEX10
Protein: p.Pro3fs
Coding: c.8del
MANE Select: NM_002617
dbSNP: rs1257198952
Type: Deletion
Location: chr1:2412495 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81

Full PEX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Peroxisome biogenesis disorder, complementation group 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 6A (Zellweger)

Similar variants

PEX10 p.Pro3Arg Uncertain significance ★ ⚠ same residue
PEX10 p.Pro3Leu Uncertain significance ★ ⚠ same residue
PEX10 p.Pro3= Likely benign ★ same residue
PEX10 c.601-38_601-37del Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Ala2fs Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Arg265fs Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Asp122fs Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Gly254fs Pathogenic/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/pex10-p-pro3fs (accessed [today's date]).

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