Is PEX13 p.Val380Phe (c.1138G>T) pathogenic?

PEX13 p.Val380Phe (c.1138G>T) is classified Uncertain significance in PEX13 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-14). AlphaMissense: likely benign (0.206); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Val380Phe (c.1138G>T)?

PEX13 p.Val380Phe (c.1138G>T) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Val380Phe (c.1138G>T) in the general population?

PEX13 p.Val380Phe (c.1138G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX13 p.Val380Phe (c.1138G>T)?

AlphaMissense predicts likely benign (score 0.206) — an in-silico prediction, not a clinical call.

PEX13 p.Val380Phe

c.1138G>T · rs1559047346 · VCV1716448

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.206 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

peroxisome biogenesis disorder 11A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.206	likely benign
REVEL	0.42	indeterminate
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.91, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 31 kb · p 0.0078 · regional, not allelic
Overall
CADD	26.1	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.Val380Phe
Coding: c.1138G>T
MANE Select: NM_002618
dbSNP: rs1559047346
Type: single nucleotide variant
Location: chr2:61048696 (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.Val380= Likely benign ★ 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
PEX13 c.913+3A>G Uncertain significance ★★ 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-val380phe (accessed [today's date]).

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