Is PEX12 p.Ala36Pro (c.106G>C) pathogenic?

PEX12 p.Ala36Pro (c.106G>C) is classified Uncertain significance in PEX12 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-26). AlphaMissense: likely pathogenic (0.9532); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder type 3B.

What condition is associated with PEX12 p.Ala36Pro (c.106G>C)?

PEX12 p.Ala36Pro (c.106G>C) is associated with peroxisome biogenesis disorder type 3B, peroxisome biogenesis disorder 3A (Zellweger) (ClinVar).

How common is PEX12 p.Ala36Pro (c.106G>C) in the general population?

PEX12 p.Ala36Pro (c.106G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX12 p.Ala36Pro (c.106G>C)?

AlphaMissense predicts likely pathogenic (score 0.9532) — an in-silico prediction, not a clinical call.

PEX12 p.Ala36Pro

c.106G>C · rs2142231624 · VCV1401041

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder type 3B

Computational evidence

Protein change
AlphaMissense	0.9532	likely pathogenic · top 7% in PEX12
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -11.87	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 2,236 bp · p 0.0034 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: PEX12
Protein: p.Ala36Pro
Coding: c.106G>C
MANE Select: NM_000286
dbSNP: rs2142231624
Type: single nucleotide variant
Location: chr17:35577916 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.58

Full PEX12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder type 3B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 3A (Zellweger)

Similar variants

PEX12 p.Ala36Ile Uncertain significance ★ same residue
PEX12 c.126+1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX12 c.680+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Arg180Ter Pathogenic ★★ same condition
PEX12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Gln111Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Gln112Ter Pathogenic/Likely pathogenic ★★ 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/pex12-p-ala36pro (accessed [today's date]).

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