Is PEX5 p.Asp401Asn (c.1201G>A) pathogenic?

PEX5 p.Asp401Asn (c.1201G>A) is classified Uncertain significance in PEX5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-21). AlphaMissense: likely benign (0.0697); Very rare (popmax 0.0011%, nfe); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Asp401Asn (c.1201G>A)?

PEX5 p.Asp401Asn (c.1201G>A) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Asp401Asn (c.1201G>A) in the general population?

PEX5 p.Asp401Asn (c.1201G>A) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about PEX5 p.Asp401Asn (c.1201G>A)?

AlphaMissense predicts likely benign (score 0.0697) — an in-silico prediction, not a clinical call.

PEX5 p.Asp401Asn

c.1201G>A · rs1945098580 · VCV1466486

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0697 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 2B

Computational evidence

Protein change
AlphaMissense	0.0697	likely benign
REVEL	0.276	benign-leaning
SaProt	LLR -9.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP -1.4, phastCons 1
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0011% European (non-Finnish) · 13/1,179,888 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000805% 13/1,614,006 alleles · very rare exomes 13/1,461,688 · genomes 0/152,318 · joint denominator

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: PEX5
Protein: p.Asp401Asn
Coding: c.1201G>A
MANE Select: NM_001351132
dbSNP: rs1945098580
Type: single nucleotide variant
Location: chr12:7208476 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB

Full PEX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX5 p.Asp401Gly Uncertain significance ★ ⚠ same residue
PEX5 c.449-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.552-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.847-2A>G Likely pathogenic ★★ same condition
PEX5 c.967-1G>A Likely pathogenic ★★ same condition
PEX5 p.Arg237Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg420Ter 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/pex5-p-asp401asn (accessed [today's date]).

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