Is PEX1 p.Arg795Ter (c.2383C>T) pathogenic?

PEX1 p.Arg795Ter (c.2383C>T) is classified Pathogenic/Likely pathogenic in PEX1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-21). Very rare (popmax 0.00659%, sas); Associated with PEX1-related disorder.

What condition is associated with PEX1 p.Arg795Ter (c.2383C>T)?

PEX1 p.Arg795Ter (c.2383C>T) is associated with PEX1-related disorder, peroxisome biogenesis disorder 1A (Zellweger), peroxisome biogenesis disorder 1B (ClinVar).

How common is PEX1 p.Arg795Ter (c.2383C>T) in the general population?

PEX1 p.Arg795Ter (c.2383C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

PEX1 p.Arg795Ter

c.2383C>T · rs61750418 · VCV188873

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

PEX1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 14 of 24
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.79	GERP -4.9
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,030 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00316% 51/1,613,770 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,172
European (non-Finnish)	0.00347%	28,777
Remaining individualsnot grpmax-eligible	0.0032%	31,235
East Asian	0.00223%	44,880
African / African-American	0.00133%	74,914

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.Arg795Ter
Coding: c.2383C>T
MANE Select: NM_000466
dbSNP: rs61750418
Type: single nucleotide variant
Location: chr7:92501923 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 795: a UniProt-annotated variant site (in pbd1a)

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

Disease context

PEX1-related disorder

Also linked: peroxisome biogenesis disorder 1A (Zellweger)peroxisome biogenesis disorder 1B peroxisome biogenesis disorder Zellweger spectrum disorders

Similar variants

PEX1 p.Arg795Gln 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
PEX1 c.1670+1G>A Pathogenic/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-arg795ter (accessed [today's date]).

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