Is PEX19 p.Ala4fs (c.9del) pathogenic?

PEX19 p.Ala4fs (c.9del) is classified Pathogenic in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). Absent from gnomAD; Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ala4fs (c.9del)?

PEX19 p.Ala4fs (c.9del) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ala4fs (c.9del) in the general population?

PEX19 p.Ala4fs (c.9del) is absent from gnomAD (gnomAD).

PEX19 p.Ala4fs

c.9del · rs2525325369 · VCV2011554

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

peroxisome biogenesis disorder 12A (Zellweger)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -0.77, phastCons 0.43

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX19
Protein: p.Ala4fs
Coding: c.9del
MANE Select: NM_002857
dbSNP: rs2525325369
Type: Deletion
Location: chr1:160285116 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 4: the 'disordered' region; the 'necessary for pex19 function on peroxisome biogenesis' region; the 'docking to the peroxisome membrane and binding to pex3' region

Full PEX19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 12A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX19 p.Ala4Asp Uncertain significance ★ ⚠ same residue
PEX19 p.Ala4Ser Uncertain significance ★ ⚠ same residue
PEX19 p.Ala4= Likely benign ★ same residue
PEX19 p.Glu88fs Pathogenic ★ same condition
PEX19 p.Glu98fs Pathogenic ★ same condition
PEX19 p.Leu133fs Likely pathogenic ★ same condition
PEX19 p.Phe29fs Pathogenic ★ same condition
PEX19 p.Met299fs 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/pex19-p-ala4fs (accessed [today's date]).

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