Is PEX2 p.Ala107Asp (c.320C>A) pathogenic?

PEX2 p.Ala107Asp (c.320C>A) is classified Uncertain significance in PEX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2002-09-08). AlphaMissense: likely pathogenic (0.9074); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 5B.

What condition is associated with PEX2 p.Ala107Asp (c.320C>A)?

PEX2 p.Ala107Asp (c.320C>A) is associated with peroxisome biogenesis disorder 5B (ClinVar).

How common is PEX2 p.Ala107Asp (c.320C>A) in the general population?

PEX2 p.Ala107Asp (c.320C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX2 p.Ala107Asp (c.320C>A)?

AlphaMissense predicts likely pathogenic (score 0.9074) — an in-silico prediction, not a clinical call.

PEX2 p.Ala107Asp

c.320C>A · rs2132044318 · VCV1704261

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9074 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 5B

Computational evidence

Protein change
AlphaMissense	0.9074	likely pathogenic · top 3% in PEX2
REVEL	0.748	pathogenic-leaning
SaProt	LLR -13.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 10	GERP 2.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic
Overall
CADD	26.9	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: PEX2
Protein: p.Ala107Asp
Coding: c.320C>A
MANE Select: NM_000318
dbSNP: rs2132044318
Type: single nucleotide variant
Location: chr8:76983859 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 107: a UniProt-annotated variant site (in pbd5a)

Full PEX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 5B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX2 p.Ala107Val Uncertain significance ★ ⚠ same residue
PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Arg119Ter Pathogenic ★★ same condition
PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln78Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Trp105Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gly161Glu Uncertain significance ★★ ⚠ same condition
PEX2 p.Gly47Ala 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/pex2-p-ala107asp (accessed [today's date]).

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