Is PEX19 p.Ala85Val (c.254C>T) pathogenic?

PEX19 p.Ala85Val (c.254C>T) is classified Conflicting classifications of pathogenicity in PEX19 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-11-23). AlphaMissense: likely benign (0.1051); Rare (popmax 0.145%, amr); Associated with peroxisome biogenesis disorder 12A (Zellweger).

What condition is associated with PEX19 p.Ala85Val (c.254C>T)?

PEX19 p.Ala85Val (c.254C>T) is associated with peroxisome biogenesis disorder 12A (Zellweger) (ClinVar).

How common is PEX19 p.Ala85Val (c.254C>T) in the general population?

PEX19 p.Ala85Val (c.254C>T) is rare (popmax 0.145%, amr) (gnomAD).

What do computational predictors say about PEX19 p.Ala85Val (c.254C>T)?

AlphaMissense predicts likely benign (score 0.1051) — an in-silico prediction, not a clinical call.

PEX19 p.Ala85Val

c.254C>T · rs11550119 · VCV500756

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1051 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 12A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.1051	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -7.83	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 8.6	GERP 2.5, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 5,570 bp · p 0.15 · regional, not allelic
Overall
CADD	28.2	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 0.145% Admixed American · 87/60,014 alleles

Filtering AF 0.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.111%

Overall 0.062% 1,001/1,614,130 alleles · rare exomes 870/1,461,852 · genomes 131/152,278 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.145%	690
European (non-Finnish)	0.0718%	1,393
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Middle Eastern	0.0165%	6,054
African / African-American	0.0147%	6,821
Finnishnot grpmax-eligible	0.00937%	10,673
South Asian	0.00549%	18,217
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,880

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.Ala85Val
Coding: c.254C>T
MANE Select: NM_002857
dbSNP: rs11550119
Type: single nucleotide variant
Location: chr1:160283036 (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.Ala85= Conflicting classifications of pathogenicity ★ same residue
PEX19 p.Ala85Glu 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

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-ala85val (accessed [today's date]).

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