Is PEX10 p.Pro126= (c.378C>G) pathogenic?

PEX10 p.Pro126= (c.378C>G) is classified Likely benign in PEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). Very rare (popmax 0.00401%, afr); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Pro126= (c.378C>G)?

PEX10 p.Pro126= (c.378C>G) is associated with Peroxisome biogenesis disorder, complementation group 7 (ClinVar).

How common is PEX10 p.Pro126= (c.378C>G) in the general population?

PEX10 p.Pro126= (c.378C>G) is very rare (popmax 0.00401%, afr) (gnomAD).

PEX10 p.Pro126=

c.378C>G · rs762783424 · VCV1558752

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

Peroxisome biogenesis disorder, complementation group 7

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 0.44	GERP -3.4, phastCons 0.015
Overall
CADD	1.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,904 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000372% 6/1,612,214 alleles · very rare exomes 4/1,460,018 · genomes 2/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,968
Admixed American	0.00167%	59,864
Remaining individualsnot grpmax-eligible	0.0016%	62,396
European (non-Finnish)	8.48e-05%	1,179,402

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.Pro126=
Coding: c.378C>G
MANE Select: NM_002617
dbSNP: rs762783424
Type: single nucleotide variant
Location: chr1:2408674 (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

Similar variants

PEX10 c.113-1G>A Likely pathogenic ★★ same condition
PEX10 c.776+1G>A Likely pathogenic ★★ same condition
PEX10 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+5G>A Uncertain significance ★★ same condition
PEX10 p.Ala150Val Uncertain significance ★★ ⚠ same condition
PEX10 p.Ala163Val Uncertain significance ★★ ⚠ same condition
PEX10 p.Ala260Asp Uncertain significance ★★ ⚠ 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-pro126 (accessed [today's date]).

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