Is PEX26 p.Pro118Arg (c.353C>G) pathogenic?

PEX26 p.Pro118Arg (c.353C>G) is classified Conflicting classifications of pathogenicity in PEX26 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-10). AlphaMissense: ambiguous (0.5234); Very rare (popmax 0.005%, amr); Associated with PEX26-related disorder.

What condition is associated with PEX26 p.Pro118Arg (c.353C>G)?

PEX26 p.Pro118Arg (c.353C>G) is associated with PEX26-related disorder, peroxisome biogenesis disorder 7A (Zellweger), peroxisome biogenesis disorder 7B (ClinVar).

How common is PEX26 p.Pro118Arg (c.353C>G) in the general population?

PEX26 p.Pro118Arg (c.353C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PEX26 p.Pro118Arg (c.353C>G)?

AlphaMissense predicts ambiguous (score 0.5234) — an in-silico prediction, not a clinical call.

PEX26 p.Pro118Arg

c.353C>G · rs61752135 · VCV449363

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

ambiguous

0.5234 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

PEX26-related disorder

Computational evidence

Protein change
AlphaMissense	0.5234	ambiguous
REVEL	0.859	moderately pathogenic-leaning
SaProt	LLR -7.10	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 4.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 9,695 bp · p 0.72 · regional, not allelic
Overall
CADD	27.9	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 0.005% Admixed American · 3/60,016 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000558% 9/1,614,188 alleles · very rare exomes 6/1,461,890 · genomes 3/152,298 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,005
African / African-American	0.00266%	37,525
South Asian	0.0011%	91,080
European (non-Finnish)	0.000254%	393,346

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.Pro118Arg
Coding: c.353C>G
MANE Select: NM_001127649
dbSNP: rs61752135
Type: single nucleotide variant
Location: chr22:18079996 (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

PEX26-related disorder

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

Similar variants

PEX26 p.Pro118Ala Uncertain significance ★★ ⚠ same residue
PEX26 p.Pro118His Uncertain significance ★★ ⚠ same residue
PEX26 p.Pro118Ser Uncertain significance ★ ⚠ same residue
PEX26 p.Pro118= Likely benign ★ 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

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-pro118arg (accessed [today's date]).

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