Is PEX19 p.Ala2= (c.6C>T) pathogenic?

PEX19 p.Ala2= (c.6C>T) is classified Likely benign in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-22). Very rare (popmax 0.00167%, amr); Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ala2= (c.6C>T)?

PEX19 p.Ala2= (c.6C>T) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ala2= (c.6C>T) in the general population?

PEX19 p.Ala2= (c.6C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

PEX19 p.Ala2=

c.6C>T · rs1227761036 · VCV2114955

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

peroxisome biogenesis disorder 12A (Zellweger)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -4.9
Overall
CADD	1.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,022 alleles

Overall 0.000186% 3/1,613,602 alleles · very rare exomes 3/1,461,308 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
African / African-American	0.00133%	75,030
European (non-Finnish)	8.48e-05%	1,179,626

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.Ala2=
Coding: c.6C>T
MANE Select: NM_002857
dbSNP: rs1227761036
Type: single nucleotide variant
Location: chr1:160285119 (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.Ala2Val 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-ala2 (accessed [today's date]).

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