Is PEX16 p.Ser295= (c.885C>T) pathogenic?

PEX16 p.Ser295= (c.885C>T) is classified Conflicting classifications of pathogenicity in PEX16 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.02%, amr); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Ser295= (c.885C>T)?

PEX16 p.Ser295= (c.885C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Ser295= (c.885C>T) in the general population?

PEX16 p.Ser295= (c.885C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

PEX16 p.Ser295=

c.885C>T · rs200415017 · VCV594434

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.2	GERP -4.1
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.02% Admixed American · 12/60,030 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00446% 72/1,614,012 alleles · ultra-rare exomes 67/1,461,650 · genomes 5/152,362 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,003
Remaining individualsnot grpmax-eligible	0.008%	12,500
European (non-Finnish)	0.00458%	21,852
African / African-American	0.00133%	75,074

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.Ser295=
Coding: c.885C>T
MANE Select: NM_004813
dbSNP: rs200415017
Type: single nucleotide variant
Location: chr11:45913821 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07
Residue 295: 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 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
PEX16 p.Arg124Trp 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-ser295 (accessed [today's date]).

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