Is PEX13 p.Pro9Arg (c.26C>G) pathogenic?

PEX13 p.Pro9Arg (c.26C>G) is classified Uncertain significance in PEX13 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.1803); Ultra-rare (popmax 0.0118%, amr); Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Pro9Arg (c.26C>G)?

PEX13 p.Pro9Arg (c.26C>G) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Pro9Arg (c.26C>G) in the general population?

PEX13 p.Pro9Arg (c.26C>G) is ultra-rare (popmax 0.0118%, amr) (gnomAD).

What do computational predictors say about PEX13 p.Pro9Arg (c.26C>G)?

AlphaMissense predicts likely benign (score 0.1803) — an in-silico prediction, not a clinical call.

PEX13 p.Pro9Arg

c.26C>G · rs764069625 · VCV289819

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1803 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder 11A (Zellweger)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1803	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -8.31	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 31 kb · p 0.0078 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% Admixed American · 6/50,938 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0053%

Overall 0.00626% 97/1,550,328 alleles · ultra-rare exomes 86/1,397,976 · genomes 11/152,352 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0118%	8,490
Remaining individualsnot grpmax-eligible	0.00999%	10,012
European (non-Finnish)	0.00706%	14,159
African / African-American	0.00273%	36,587
Finnishnot grpmax-eligible	0.0017%	58,808
South Asian	0.00119%	83,966

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: PEX13
Protein: p.Pro9Arg
Coding: c.26C>G
MANE Select: NM_002618
dbSNP: rs764069625
Type: single nucleotide variant
Location: chr2:61017785 (GRCh38)

Full PEX13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 11A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/pex13-p-pro9arg (accessed [today's date]).

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