Is PEX19 p.Ser134fs (c.398dup) pathogenic?

PEX19 p.Ser134fs (c.398dup) is classified Pathogenic in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-01). Very rare (popmax 0.000339%, nfe); Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ser134fs (c.398dup)?

PEX19 p.Ser134fs (c.398dup) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ser134fs (c.398dup) in the general population?

PEX19 p.Ser134fs (c.398dup) is very rare (popmax 0.000339%, nfe) (gnomAD).

PEX19 p.Ser134fs

c.398dup · rs1240816309 · VCV1444009

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.09	GERP 0.28, phastCons 0.81
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,994 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,046 alleles · very rare exomes 3/1,461,822 · genomes 1/152,224 · joint denominator

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: PEX19
Protein: p.Ser134fs
Coding: c.398dup
MANE Select: NM_002857
dbSNP: rs1240816309
Type: Duplication
Location: chr1:160282450 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB

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.Ser134= Conflicting classifications of pathogenicity ★ same residue
PEX19 p.Met255fs Conflicting classifications of pathogenicity ★ same condition
PEX19 c.346+2T>C Likely pathogenic ★★ same condition
PEX19 p.Leu94Ter Likely pathogenic ★★ same condition
PEX19 p.Lys193Ter Pathogenic/Likely pathogenic ★★ same condition
PEX19 p.Ser54Leu Pathogenic ★★ ⚠ same condition
PEX19 c.*1335G>T Uncertain significance ★★ same condition
PEX19 c.*864C>T 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-ser134fs (accessed [today's date]).

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