Is PEX13 p.Pro22Ser (c.64C>T) pathogenic?

PEX13 p.Pro22Ser (c.64C>T) is classified Uncertain significance in PEX13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-20). AlphaMissense: likely benign (0.0732); Very rare (popmax 0.00714%, sas); Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Pro22Ser (c.64C>T)?

PEX13 p.Pro22Ser (c.64C>T) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Pro22Ser (c.64C>T) in the general population?

PEX13 p.Pro22Ser (c.64C>T) is very rare (popmax 0.00714%, sas) (gnomAD).

What do computational predictors say about PEX13 p.Pro22Ser (c.64C>T)?

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

PEX13 p.Pro22Ser

c.64C>T · rs1466677796 · VCV1353244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00714%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 11A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.0732	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	17.64	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 0.00714% South Asian · 6/84,044 alleles

Filtering AF 0.00306% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.000501% 7/1,398,186 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00714%	14,007
European (non-Finnish)	8.72e-05%	1,146,806

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.Pro22Ser
Coding: c.64C>T
MANE Select: NM_002618
dbSNP: rs1466677796
Type: single nucleotide variant
Location: chr2:61017823 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 3 PDB
Residue 22: the 'disordered' region

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

Similar variants

PEX13 p.Pro22= Likely benign ★ same residue
PEX13 p.Pro22Leu Uncertain significance ★ ⚠ same residue
PEX13 p.Arg16Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg226Ter Pathogenic ★★ same condition
PEX13 p.Gln131Ter Pathogenic ★★ same condition
PEX13 p.Glu123Ter Pathogenic ★★ same condition
PEX13 p.Tyr155Ter 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/pex13-p-pro22ser (accessed [today's date]).

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