Is PEX3 p.Arg286Ter (c.856C>T) pathogenic?

PEX3 p.Arg286Ter (c.856C>T) is classified Pathogenic in PEX3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-25). Very rare (popmax 0.0011%, sas).

How common is PEX3 p.Arg286Ter (c.856C>T) in the general population?

PEX3 p.Arg286Ter (c.856C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

PEX3 p.Arg286Ter

c.856C>T · rs147556993 · VCV598102

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 12
Splicing
SpliceAI	Δ0.71	acceptor loss, 37 bp away · masked 0 · deltas
Pangolin	Δ0.38	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.7	GERP 1, phastCons 1
Overall
CADD	38.0	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 0.0011% South Asian · 1/90,500 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000252% 4/1,589,040 alleles · very rare exomes 4/1,437,028 · genomes 0/152,012 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,500
European (non-Finnish)	0.000259%	385,847

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.Arg286Ter
Coding: c.856C>T
MANE Select: NM_003630
dbSNP: rs147556993
Type: single nucleotide variant
Location: chr6:143479113 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 286: an α-helix

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

Similar variants

PEX3 p.Arg286= Benign/Likely benign ★★ same residue
PEX3 p.Arg286Gln Uncertain significance ★ ⚠ same residue
PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same type
PEX3 c.942-1G>T Likely pathogenic ★★ same type
PEX3 p.Arg256Ter Pathogenic/Likely pathogenic ★★ same type
PEX3 p.Trp6Ter Pathogenic ★★ same type
PEX3 c.818+3A>G Uncertain significance ★★ same type
PEX3 c.-96G>T Uncertain significance ★★ 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-arg286ter (accessed [today's date]).

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