Is PEX13 p.Arg16Ter (c.46C>T) pathogenic?

PEX13 p.Arg16Ter (c.46C>T) is classified Pathogenic/Likely pathogenic in PEX13 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). Very rare (popmax 0.00384%, nfe); Associated with PEX13-related disorder.

What condition is associated with PEX13 p.Arg16Ter (c.46C>T)?

PEX13 p.Arg16Ter (c.46C>T) is associated with PEX13-related disorder, peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Arg16Ter (c.46C>T) in the general population?

PEX13 p.Arg16Ter (c.46C>T) is very rare (popmax 0.00384%, nfe) (gnomAD).

PEX13 p.Arg16Ter

c.46C>T · rs1178588746 · VCV1372243

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 0.00384%, nfe)

Conditions

PEX13-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 1 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.5, phastCons 1
Overall
CADD	37.0	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 0.00384% European (non-Finnish) · 44/1,146,892 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00259%

Overall 0.00297% 46/1,550,436 alleles · very rare exomes 44/1,398,228 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00384%	26,066
Remaining individualsnot grpmax-eligible	0.00333%	30,036

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: PEX13
Protein: p.Arg16Ter
Coding: c.46C>T
MANE Select: NM_002618
dbSNP: rs1178588746
Type: single nucleotide variant
Location: chr2:61017805 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 3 PDB
Residue 16: the 'disordered' region

Full PEX13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PEX13-related disorder

Also linked: peroxisome biogenesis disorder 11A (Zellweger)

Similar variants

PEX13 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg226Ter Pathogenic ★★ same condition
PEX13 p.Gln131Ter Pathogenic ★★ same condition
PEX13 p.Glu123Ter Pathogenic ★★ same condition
PEX13 p.Tyr155Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 c.913+3A>G Uncertain significance ★★ same condition
PEX13 p.Ala302Gly Uncertain significance ★★ same condition
PEX13 p.Ala364Thr 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/pex13-p-arg16ter (accessed [today's date]).

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