Is PEX16 p.Leu35= (c.103C>T) pathogenic?

PEX16 p.Leu35= (c.103C>T) is classified Likely benign in PEX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Very rare (popmax 0.00417%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Leu35= (c.103C>T)?

PEX16 p.Leu35= (c.103C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Leu35= (c.103C>T) in the general population?

PEX16 p.Leu35= (c.103C>T) is very rare (popmax 0.00417%, nfe) (gnomAD).

PEX16 p.Leu35=

c.103C>T · rs1427588700 · VCV1559044

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00417%, nfe)

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Overall
CADD	14.76	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00417% European (non-Finnish) · 48/1,150,932 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.00314% 49/1,558,502 alleles · very rare exomes 44/1,406,280 · genomes 5/152,222 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00417%	23,978
Admixed American	0.00193%	51,916

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.Leu35=
Coding: c.103C>T
MANE Select: NM_004813
dbSNP: rs1427588700
Type: single nucleotide variant
Location: chr11:45917709 (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.Leu35Val 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
PEX16 p.Ala114Thr 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-leu35 (accessed [today's date]).

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