Is PEX19 p.Ala85= (c.255G>A) pathogenic?

PEX19 p.Ala85= (c.255G>A) is classified Conflicting classifications of pathogenicity in PEX19 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.147%, afr); Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ala85= (c.255G>A)?

PEX19 p.Ala85= (c.255G>A) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ala85= (c.255G>A) in the general population?

PEX19 p.Ala85= (c.255G>A) is rare (popmax 0.147%, afr) (gnomAD).

PEX19 p.Ala85=

c.255G>A · rs150928521 · VCV288371

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.147%, afr)

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 -9.6	GERP -5
Overall
CADD	3.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.147% African / African-American · 110/75,048 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00781% 126/1,614,194 alleles · rare exomes 63/1,461,876 · genomes 63/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.147%	682
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.01%	10,004
South Asian	0.0011%	91,080
European (non-Finnish)	8.47e-05%	1,180,040

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.Ala85=
Coding: c.255G>A
MANE Select: NM_002857
dbSNP: rs150928521
Type: single nucleotide variant
Location: chr1:160283035 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB
Residue 85: a UniProt-annotated variant site (found in patients with progressive myoclonus epilepsy and dementia; uncertain significance); 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 p.Ala85Glu Uncertain significance ★ ⚠ same residue
PEX19 p.Ala85Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-ala85 (accessed [today's date]).

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