Is PEX13 p.Val348Ile (c.1042G>A) pathogenic?

PEX13 p.Val348Ile (c.1042G>A) is classified Uncertain significance in PEX13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-04). AlphaMissense: likely benign (0.0585); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Val348Ile (c.1042G>A)?

PEX13 p.Val348Ile (c.1042G>A) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Val348Ile (c.1042G>A) in the general population?

PEX13 p.Val348Ile (c.1042G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX13 p.Val348Ile (c.1042G>A)?

AlphaMissense predicts likely benign (score 0.0585) — an in-silico prediction, not a clinical call.

PEX13 p.Val348Ile

c.1042G>A · rs1680746855 · VCV2106103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0585 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 11A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.0585	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.11	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 2.3	GERP -3.5, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 31 kb · p 0.0078 · regional, not allelic
Overall
CADD	9.503	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX13
Protein: p.Val348Ile
Coding: c.1042G>A
MANE Select: NM_002618
dbSNP: rs1680746855
Type: single nucleotide variant
Location: chr2:61048600 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 3 PDB

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.Val348= Benign/Likely benign ★★ same residue
PEX13 p.Val348Leu 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-val348ile (accessed [today's date]).

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