Is PEX3 p.Arg256Ter (c.766C>T) pathogenic?

PEX3 p.Arg256Ter (c.766C>T) is classified Pathogenic/Likely pathogenic in PEX3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-26). Very rare (popmax 0.000126%); Associated with PEX3-related disorder.

What condition is associated with PEX3 p.Arg256Ter (c.766C>T)?

PEX3 p.Arg256Ter (c.766C>T) is associated with PEX3-related disorder (ClinVar).

How common is PEX3 p.Arg256Ter (c.766C>T) in the general population?

PEX3 p.Arg256Ter (c.766C>T) is very rare (popmax 0.000126%) (gnomAD).

PEX3 p.Arg256Ter

c.766C>T · VCV4742849

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000126%)

Conditions

PEX3-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 9 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 0.72, phastCons 1
Overall
CADD	39.0	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 0.000126%

Overall 0.000126% 2/1,589,802 alleles · very rare exomes 1/1,437,760 · genomes 1/152,042 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00162%	61,692
Finnishnot grpmax-eligible	0.00157%	63,778

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PEX3
Protein: p.Arg256Ter
Coding: c.766C>T
MANE Select: NM_003630
Type: single nucleotide variant
Location: chr6:143474804 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 256: an α-helix

Full PEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PEX3-related disorder

Similar variants

PEX3 c.942-1G>T Likely pathogenic ★★ same condition
PEX3 c.579-1G>A Likely pathogenic ★ same condition
PEX3 p.Gly331Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
PEX3 p.Ser273Asn Uncertain significance ⚠ same condition
PEX3 p.Phe18= Likely benign same condition
PEX3 p.Met81fs Likely pathogenic ★ same condition
PEX3 p.Pro158fs Likely pathogenic ★ same condition
PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same type

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/pex3-p-arg256ter (accessed [today's date]).

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