Is PEX19 p.Pro39Ser (c.115C>T) pathogenic?

PEX19 p.Pro39Ser (c.115C>T) is classified Conflicting classifications of pathogenicity in PEX19 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-21). AlphaMissense: likely benign (0.0601); Rare (popmax 0.676%, mid); Associated with Inborn genetic diseases.

What condition is associated with PEX19 p.Pro39Ser (c.115C>T)?

PEX19 p.Pro39Ser (c.115C>T) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Pro39Ser (c.115C>T) in the general population?

PEX19 p.Pro39Ser (c.115C>T) is rare (popmax 0.676%, mid) (gnomAD).

What do computational predictors say about PEX19 p.Pro39Ser (c.115C>T)?

AlphaMissense predicts likely benign (score 0.0601) — an in-silico prediction, not a clinical call.

PEX19 p.Pro39Ser

c.115C>T · rs144256391 · VCV499937

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0601 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.676%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0601	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -6.13	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 1.8	GERP -0.57, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 5,570 bp · p 0.15 · regional, not allelic
Overall
CADD	16.65	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.676% Middle Eastern · 41/6,062 alleles

Filtering AF 0.512% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.455%

Overall 0.0238% 384/1,614,152 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.676%	148
Remaining individualsnot grpmax-eligible	0.0752%	1,330
Admixed American	0.055%	1,819
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,692
European (non-Finnish)	0.0201%	4,979
South Asian	0.00988%	10,121
African / African-American	0.00666%	15,008
Finnishnot grpmax-eligible	0.00156%	64,032

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.Pro39Ser
Coding: c.115C>T
MANE Select: NM_002857
dbSNP: rs144256391
Type: single nucleotide variant
Location: chr1:160283595 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 39: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 12A (Zellweger)

Similar variants

PEX19 p.Pro39Ala Uncertain significance ★★ ⚠ same residue
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

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-pro39ser (accessed [today's date]).

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