Is PEX16 p.Tyr291= (c.873T>C) pathogenic?

PEX16 p.Tyr291= (c.873T>C) is classified Benign/Likely benign in PEX16 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 92.5%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with peroxisome biogenesis disorder 8A (Zellweger).

What condition is associated with PEX16 p.Tyr291= (c.873T>C)?

PEX16 p.Tyr291= (c.873T>C) is associated with peroxisome biogenesis disorder 8A (Zellweger), peroxisome biogenesis disorder 8B, peroxisome biogenesis disorder (ClinVar).

PEX16 p.Tyr291=

Q: How common is PEX16 p.Tyr291= (c.873T>C) in the general population?

PEX16 p.Tyr291= (c.873T>C) is common (popmax 92.5%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.873T>C · rs1132349 · VCV259547

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 92.5%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

peroxisome biogenesis disorder 8A (Zellweger)

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 -4.5	GERP -4.4
Overall
CADD	0.045	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 92.5% European (non-Finnish) · 1,091,236/1,179,936 alleles

Filtering AF 92.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 92.3%

Overall 87.7% 1,414,403/1,613,690 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	94.5%	1
Amishnot grpmax-eligible	92.8%	1
European (non-Finnish)grpmax	92.5%	1
Middle Eastern	87%	1
Ashkenazi Jewishnot grpmax-eligible	86.9%	1
South Asian	86.7%	1
Remaining individualsnot grpmax-eligible	86.1%	1
Admixed American	61.8%	2
African / African-American	58.4%	2
East Asian	38.8%	3

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr291=
Coding: c.873T>C
MANE Select: NM_004813
dbSNP: rs1132349
Type: single nucleotide variant
Location: chr11:45913833 (GRCh38)
Gene constraint: LOEUF 0.957 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.07
Residue 291: the 'interaction with pex19' region

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

Disease context

peroxisome biogenesis disorder 8A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 8B peroxisome biogenesis disorder

Similar variants

PEX16 p.Tyr291Asn 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-tyr291 (accessed [today's date]).

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