Is PEX16 p.Cys91= (c.273C>T) pathogenic?

PEX16 p.Cys91= (c.273C>T) is classified Conflicting classifications of pathogenicity in PEX16 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-13). Ultra-rare (popmax 0.0164%, mid); Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Cys91= (c.273C>T)?

PEX16 p.Cys91= (c.273C>T) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Cys91= (c.273C>T) in the general population?

PEX16 p.Cys91= (c.273C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

PEX16 p.Cys91=

c.273C>T · rs146476007 · VCV594810

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

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
Constraint at this position
Conservation	phyloP -0.77	GERP -4.3
Overall
CADD	7.561	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.0013% 21/1,613,484 alleles · ultra-rare exomes 17/1,461,576 · genomes 4/151,908 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.00333%	29,997
Remaining individualsnot grpmax-eligible	0.0032%	31,236
African / African-American	0.00267%	37,414
East Asian	0.00223%	44,812
European (non-Finnish)	0.0011%	90,752

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.Cys91=
Coding: c.273C>T
MANE Select: NM_004813
dbSNP: rs146476007
Type: single nucleotide variant
Location: chr11:45915789 (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 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-cys91 (accessed [today's date]).

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