Is PEX26 p.Ala10= (c.30C>T) pathogenic?

PEX26 p.Ala10= (c.30C>T) is classified Likely benign in PEX26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). Very rare (popmax 0.00268%, afr); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Ala10= (c.30C>T)?

PEX26 p.Ala10= (c.30C>T) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Ala10= (c.30C>T) in the general population?

PEX26 p.Ala10= (c.30C>T) is very rare (popmax 0.00268%, afr) (gnomAD).

PEX26 p.Ala10=

c.30C>T · rs774393110 · VCV1674483

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00268%, 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 -0.53	GERP -0.77
Overall
CADD	10.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00268% African / African-American · 2/74,708 alleles

Filtering AF 0.000444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00025% 4/1,598,744 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00268%	37,354
South Asian	0.00112%	89,484
European (non-Finnish)	8.51e-05%	1,174,811

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.Ala10=
Coding: c.30C>T
MANE Select: NM_001127649
dbSNP: rs774393110
Type: single nucleotide variant
Location: chr22:18078406 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87
Residue 10: the 'disordered' region

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 p.Ala10Val Uncertain significance ★★ ⚠ same residue
PEX26 p.Ala10fs Pathogenic ★ same residue
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

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-ala10 (accessed [today's date]).

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