Is PEX19 p.Ala2Val (c.5C>T) pathogenic?

PEX19 p.Ala2Val (c.5C>T) is classified Uncertain significance in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). AlphaMissense: likely benign (0.3385); Very rare (popmax 0.00167%, amr); Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ala2Val (c.5C>T)?

PEX19 p.Ala2Val (c.5C>T) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ala2Val (c.5C>T) in the general population?

PEX19 p.Ala2Val (c.5C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PEX19 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.3385) — an in-silico prediction, not a clinical call.

PEX19 p.Ala2Val

c.5C>T · rs1307265959 · VCV1514640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3385 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder 12A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.3385	likely benign
REVEL	0.297	indeterminate
SaProt	LLR -11.30	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 5,570 bp · p 0.15 · regional, not allelic
Overall
CADD	25.7	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 0.00167% Admixed American · 1/60,030 alleles

Overall 0.000124% 2/1,613,330 alleles · very rare exomes 2/1,460,988 · genomes 0/152,342 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,030
European (non-Finnish)	8.48e-05%	1,179,391

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_002857
dbSNP: rs1307265959
Type: single nucleotide variant
Location: chr1:160285120 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 2: the 'disordered' region; the 'necessary for pex19 function on peroxisome biogenesis' region; the 'docking to the peroxisome membrane and binding to pex3' region; a modified residue (n-acetylalanine)

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.Ala2= Likely benign ★ 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-ala2val (accessed [today's date]).

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