Is PEX16 p.Ala37= (c.111A>G) pathogenic?

PEX16 p.Ala37= (c.111A>G) is classified Uncertain significance in PEX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 8B.

What condition is associated with PEX16 p.Ala37= (c.111A>G)?

PEX16 p.Ala37= (c.111A>G) is associated with peroxisome biogenesis disorder 8B (ClinVar).

How common is PEX16 p.Ala37= (c.111A>G) in the general population?

PEX16 p.Ala37= (c.111A>G) is absent from gnomAD v4.1 (gnomAD).

PEX16 p.Ala37=

c.111A>G · VCV4856635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

peroxisome biogenesis disorder 8B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.91	donor loss, 1 bp away · masked 0 · deltas
Pangolin	Δ0.76	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.1	GERP 2.1, phastCons 1
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX16
Protein: p.Ala37=
Coding: c.111A>G
MANE Select: NM_004813
Type: single nucleotide variant
Location: chr11:45917701 (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 8B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX16 p.Arg287Cys Pathogenic/Likely pathogenic ★★ same condition
PEX16 p.Arg293Cys Uncertain significance ★★ ⚠ same condition
PEX16 c.542-16C>T Benign/Likely benign ★★ same condition
PEX16 c.*65T>C Benign/Likely benign ★★ same condition
PEX16 p.Tyr291= Benign/Likely benign ★★ same condition
PEX16 p.Val254Leu Benign/Likely benign ★★ same condition
PEX16 p.Arg227Gly Likely pathogenic ★ same condition
PEX16 c.695-6C>T Conflicting classifications of pathogenicity ★ 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-ala37 (accessed [today's date]).

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