Is PEX16 p.Phe332= (c.996C>T) pathogenic?

PEX16 p.Phe332= (c.996C>T) is classified Conflicting classifications of pathogenicity in PEX16 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-01). Very rare (popmax 0.00203%, nfe); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Phe332= (c.996C>T)?

PEX16 p.Phe332= (c.996C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Phe332= (c.996C>T) in the general population?

PEX16 p.Phe332= (c.996C>T) is very rare (popmax 0.00203%, nfe) (gnomAD).

PEX16 p.Phe332=

c.996C>T · rs200546977 · VCV593618

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

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	Δ0.23	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 8.6	GERP 0.31, phastCons 1
Overall
CADD	8.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,179,912 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00155% 25/1,613,658 alleles · very rare exomes 24/1,461,502 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00203%	49,163
Remaining individualsnot grpmax-eligible	0.0016%	62,468

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.Phe332=
Coding: c.996C>T
MANE Select: NM_004813
dbSNP: rs200546977
Type: single nucleotide variant
Location: chr11:45910269 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07
Residue 332: the 'interaction with pex19' region

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.Phe332_Tyr333del 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-phe332 (accessed [today's date]).

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