Is PEX26 p.Val106= (c.318C>G) pathogenic?

PEX26 p.Val106= (c.318C>G) is classified Conflicting classifications of pathogenicity in PEX26 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-10-13). Ultra-rare (popmax 0.0868%, afr); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Val106= (c.318C>G)?

PEX26 p.Val106= (c.318C>G) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Val106= (c.318C>G) in the general population?

PEX26 p.Val106= (c.318C>G) is ultra-rare (popmax 0.0868%, afr) (gnomAD).

PEX26 p.Val106=

c.318C>G · rs142072315 · VCV593904

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0868%, afr)

Conditions

peroxisome biogenesis disorder 7A (Zellweger)

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 0.007	GERP -0.32, phastCons 0.9
Overall
CADD	5.469	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0868% African / African-American · 65/74,906 alleles

Filtering AF 0.0698% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0637%

Overall 0.00936% 151/1,613,948 alleles · ultra-rare exomes 115/1,461,806 · genomes 36/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0868%	1,152
European (non-Finnish)	0.00678%	14,750
Remaining individualsnot grpmax-eligible	0.0048%	20,828
Admixed American	0.00333%	29,997
Finnishnot grpmax-eligible	0.00156%	64,024

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: PEX26
Protein: p.Val106=
Coding: c.318C>G
MANE Select: NM_001127649
dbSNP: rs142072315
Type: single nucleotide variant
Location: chr22:18079961 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87

Full PEX26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 7A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 7B

Similar variants

PEX26 c.230+1G>T Pathogenic ★★ same condition
PEX26 c.667+2T>C Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Arg98Trp Pathogenic/Likely pathogenic ★★ same condition
PEX26 p.Gln146Ter Pathogenic ★★ same condition
PEX26 p.Gly89Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
PEX26 p.Trp62Ter Pathogenic/Likely pathogenic ★★ same condition
PEX26 c.230+3A>G 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/pex26-p-val106 (accessed [today's date]).

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