Is PEX19 p.Ala80Val (c.239C>T) pathogenic?

PEX19 p.Ala80Val (c.239C>T) is classified Uncertain significance in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely pathogenic (0.651); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ala80Val (c.239C>T)?

PEX19 p.Ala80Val (c.239C>T) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ala80Val (c.239C>T) in the general population?

PEX19 p.Ala80Val (c.239C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX19 p.Ala80Val (c.239C>T)?

AlphaMissense predicts likely pathogenic (score 0.651) — an in-silico prediction, not a clinical call.

PEX19 p.Ala80Val

c.239C>T · rs1657843456 · VCV2163357

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.651 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 12A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.651	likely pathogenic
REVEL	0.185	benign-leaning
SaProt	LLR -6.35	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 5,570 bp · p 0.15 · regional, not allelic
Overall
CADD	29.1	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

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.Ala80Val
Coding: c.239C>T
MANE Select: NM_002857
dbSNP: rs1657843456
Type: single nucleotide variant
Location: chr1:160283051 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 80: the 'necessary for pex19 function on peroxisome biogenesis' region

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-ala80val (accessed [today's date]).

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