Is PEX26 p.Ala69= (c.207C>T) pathogenic?

PEX26 p.Ala69= (c.207C>T) is classified Conflicting classifications of pathogenicity in PEX26 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0689%, nfe); Associated with peroxisome biogenesis disorder 7A (Zellweger).

What condition is associated with PEX26 p.Ala69= (c.207C>T)?

PEX26 p.Ala69= (c.207C>T) is associated with peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Ala69= (c.207C>T) in the general population?

PEX26 p.Ala69= (c.207C>T) is ultra-rare (popmax 0.0689%, nfe) (gnomAD).

PEX26 p.Ala69=

c.207C>T · rs375516973 · VCV340751

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0689%, nfe)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.16	GERP 2.1
Overall
CADD	8.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0689% European (non-Finnish) · 810/1,175,818 alleles

Filtering AF 0.065% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0634%

Overall 0.0534% 855/1,600,096 alleles · ultra-rare exomes 813/1,447,868 · genomes 42/152,228 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0689%	1,452
Remaining individualsnot grpmax-eligible	0.0564%	1,772
African / African-American	0.0107%	9,353
Finnishnot grpmax-eligible	0.0017%	58,686
Admixed American	0.0017%	58,862

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.Ala69=
Coding: c.207C>T
MANE Select: NM_001127649
dbSNP: rs375516973
Type: single nucleotide variant
Location: chr22:18078583 (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 p.Ala69Pro Uncertain significance ★ ⚠ same residue
PEX26 p.Ala69Thr Uncertain significance ★ ⚠ 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-ala69 (accessed [today's date]).

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