Is PEX16 p.Ala121= (c.363T>C) pathogenic?

PEX16 p.Ala121= (c.363T>C) is classified Likely benign in PEX16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder.

What condition is associated with PEX16 p.Ala121= (c.363T>C)?

PEX16 p.Ala121= (c.363T>C) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX16 p.Ala121= (c.363T>C) in the general population?

PEX16 p.Ala121= (c.363T>C) is absent from gnomAD v4.1 (gnomAD).

PEX16 p.Ala121=

c.363T>C · VCV3726089

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	all four deltas below 0.2 · A>T here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -4.3
Overall
CADD	2.245	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.Ala121=
Coding: c.363T>C
MANE Select: NM_004813
Type: single nucleotide variant
Location: chr11:45915565 (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-ala121 (accessed [today's date]).

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