Is PEX19 p.Ala44Pro (c.130G>C) pathogenic?

PEX19 p.Ala44Pro (c.130G>C) is classified Uncertain significance in PEX19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-10). AlphaMissense: likely benign (0.075); Absent from gnomAD v4.1; Associated with PEX19-related disorder.

What condition is associated with PEX19 p.Ala44Pro (c.130G>C)?

PEX19 p.Ala44Pro (c.130G>C) is associated with PEX19-related disorder (ClinVar).

How common is PEX19 p.Ala44Pro (c.130G>C) in the general population?

PEX19 p.Ala44Pro (c.130G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX19 p.Ala44Pro (c.130G>C)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

PEX19 p.Ala44Pro

c.130G>C · rs745665641 · VCV3033936

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PEX19-related disorder

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.41	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 0.11	GERP -1.7, phastCons 0.002
Regional constraint	o/e 1.08	unconstrained · MANE · 5,570 bp · p 0.15 · regional, not allelic
Overall
CADD	19.97	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: PEX19
Protein: p.Ala44Pro
Coding: c.130G>C
MANE Select: NM_002857
dbSNP: rs745665641
Type: single nucleotide variant
Location: chr1:160283580 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 44: 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

PEX19-related disorder

Similar variants

PEX19 p.Ala44Thr Uncertain significance ★ ⚠ same residue
PEX19 p.Ala44= Likely benign ★ same residue
PEX19 c.346+2T>C Likely pathogenic ★★ same condition
PEX19 p.Cys8Tyr Uncertain significance ★★ ⚠ same condition
PEX19 p.Ser149Leu Uncertain significance ★★ ⚠ same condition
PEX19 p.Ser286Trp Uncertain significance ★★ ⚠ same condition
PEX19 c.432+2T>C Likely pathogenic ★ same condition
PEX19 p.Thr154Ser 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-ala44pro (accessed [today's date]).

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