Is PEX16 p.Ile141= (c.423C>T) pathogenic?

PEX16 p.Ile141= (c.423C>T) is classified Likely benign in PEX16 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-06). Ultra-rare (popmax 0.0133%, afr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Ile141= (c.423C>T)?

PEX16 p.Ile141= (c.423C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Ile141= (c.423C>T) in the general population?

PEX16 p.Ile141= (c.423C>T) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

PEX16 p.Ile141=

c.423C>T · rs754277134 · VCV1130485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Conditions

peroxisome biogenesis disorder

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
Pangolin	Δ0.20	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.59	GERP -3.5
Overall
CADD	9.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% African / African-American · 10/74,936 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.00136% 22/1,614,040 alleles · ultra-rare exomes 12/1,461,844 · genomes 10/152,196 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,494
Remaining individualsnot grpmax-eligible	0.0032%	31,245
East Asian	0.00223%	44,884
Admixed American	0.00167%	60,010
European (non-Finnish)	0.000678%	147,503

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: PEX16
Protein: p.Ile141=
Coding: c.423C>T
MANE Select: NM_004813
dbSNP: rs754277134
Type: single nucleotide variant
Location: chr11:45915505 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07

Full PEX16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX16 p.Ile141Val Uncertain significance ★★ ⚠ same residue
PEX16 p.Ile141Leu Uncertain significance ★ ⚠ same residue
PEX16 c.888-1G>C Likely pathogenic ★★ same condition
PEX16 p.Arg176Ter Pathogenic ★★ same condition
PEX16 p.Arg227Trp Likely pathogenic ★★ same condition
PEX16 p.Arg287Cys Pathogenic/Likely pathogenic ★★ same condition
PEX16 p.Arg287His Pathogenic/Likely pathogenic ★★ ⚠ same condition
PEX16 c.225+3G>A 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/pex16-p-ile141 (accessed [today's date]).

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