Is PEX1 p.Arg819= (c.2457C>T) pathogenic?

PEX1 p.Arg819= (c.2457C>T) is classified Likely benign in PEX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.078%, sas); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Arg819= (c.2457C>T)?

PEX1 p.Arg819= (c.2457C>T) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Arg819= (c.2457C>T) in the general population?

PEX1 p.Arg819= (c.2457C>T) is ultra-rare (popmax 0.078%, sas) (gnomAD).

How is Zellweger syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PEX1 p.Arg819=

c.2457C>T · rs779477506 · VCV1078260

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, sas)

Conditions

Zellweger spectrum disorders

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 -0.71	GERP -1
Overall
CADD	2.559	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.078% South Asian · 71/91,080 alleles

Filtering AF 0.0633% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.058%

Overall 0.00551% 89/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.078%	1,283
Middle Eastern	0.0329%	3,041
Remaining individualsnot grpmax-eligible	0.0048%	20,827
East Asian	0.00446%	22,441
Admixed American	0.00167%	59,986
African / African-American	0.00134%	74,894
European (non-Finnish)	0.000763%	131,099

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: PEX1
Protein: p.Arg819=
Coding: c.2457C>T
MANE Select: NM_000466
dbSNP: rs779477506
Type: single nucleotide variant
Location: chr7:92501633 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 819: a UniProt-annotated variant site (in pbd1a)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Zellweger spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Zellweger syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PEX1 p.Arg819Cys Uncertain significance ★★ ⚠ same residue
PEX1 p.Arg819His Uncertain significance ★ ⚠ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ 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/pex1-p-arg819 (accessed [today's date]).

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