Is PEX19 p.Ser191= (c.573A>C) pathogenic?

PEX19 p.Ser191= (c.573A>C) is classified Likely benign in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-02). Very rare (popmax 0.00314%, nfe); Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ser191= (c.573A>C)?

PEX19 p.Ser191= (c.573A>C) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ser191= (c.573A>C) in the general population?

PEX19 p.Ser191= (c.573A>C) is very rare (popmax 0.00314%, nfe) (gnomAD).

PEX19 p.Ser191=

c.573A>C · rs373136197 · VCV1979205

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Conditions

peroxisome biogenesis disorder 12A (Zellweger)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.351	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -5
Overall
CADD	3.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00314% European (non-Finnish) · 37/1,179,958 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00254% 41/1,613,964 alleles · very rare exomes 40/1,461,804 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)grpmax	0.00314%	31,891
African / African-American	0.00133%	74,924

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser191=
Coding: c.573A>C
MANE Select: NM_002857
dbSNP: rs373136197
Type: single nucleotide variant
Location: chr1:160282060 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 191: an α-helix

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 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
PEX19 p.Ala14Pro Uncertain significance ★★ ⚠ same condition
PEX19 p.Ala234Ser 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-ser191 (accessed [today's date]).

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