Is PEX26 p.Ser296Pro (c.886T>C) pathogenic?

PEX26 p.Ser296Pro (c.886T>C) is classified Uncertain significance in PEX26 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-03). AlphaMissense: likely benign (0.0732); Ultra-rare (popmax 0.0334%, afr); Associated with Inborn genetic diseases.

What condition is associated with PEX26 p.Ser296Pro (c.886T>C)?

PEX26 p.Ser296Pro (c.886T>C) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Ser296Pro (c.886T>C) in the general population?

PEX26 p.Ser296Pro (c.886T>C) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

What do computational predictors say about PEX26 p.Ser296Pro (c.886T>C)?

AlphaMissense predicts likely benign (score 0.0732) — an in-silico prediction, not a clinical call.

PEX26 p.Ser296Pro

c.886T>C · rs143243841 · VCV497602

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0732 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0732	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.23	GERP -4
Regional constraint	o/e 0.98	unconstrained · MANE · 9,695 bp · p 0.72 · regional, not allelic
Overall
CADD	13.16	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% African / African-American · 25/74,904 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00155% 25/1,613,150 alleles · ultra-rare exomes 14/1,461,032 · genomes 11/152,118 · joint denominator

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.Ser296Pro
Coding: c.886T>C
MANE Select: NM_001127649
dbSNP: rs143243841
Type: single nucleotide variant
Location: chr22:18088043 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 7A (Zellweger)peroxisome biogenesis disorder 7B

Similar variants

PEX26 p.Ser296Tyr 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
PEX26 p.Trp62Ter 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-ser296pro (accessed [today's date]).

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