Is PEX5 p.Val75fs (c.220del) pathogenic?

PEX5 p.Val75fs (c.220del) is classified Likely pathogenic in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-19). Associated with PEX5-related disorder.

What condition is associated with PEX5 p.Val75fs (c.220del)?

PEX5 p.Val75fs (c.220del) is associated with PEX5-related disorder (ClinVar).

PEX5 p.Val75fs

c.220del · VCV4915537

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

PEX5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.19	GERP -2.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PEX5
Protein: p.Val75fs
Coding: c.220del
MANE Select: NM_001351132
Type: Deletion
Location: chr12:7191259 (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

PEX5-related disorder

Similar variants

PEX5 c.147+27del Likely pathogenic ★ same condition
PEX5 c.147+32_147+121del Conflicting classifications of pathogenicity ★ same condition
PEX5 p.Val75Ala Uncertain significance ★ ⚠ same residue
PEX5 p.Val75= Likely benign ★ same residue
PEX5 p.Trp184Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.147+11_147+56delinsG Likely pathogenic ★ same condition
PEX5 p.Leu463fs Likely pathogenic ★ same condition
PEX5 p.Ile222Thr 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/pex5-p-val75fs (accessed [today's date]).

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