Is WDR45 p.Arg111fs (c.332_338del) pathogenic?

WDR45 p.Arg111fs (c.332338del) is classified Pathogenic in WDR45 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-23). Absent from gnomAD; Associated with neurodegeneration with brain iron accumulation 5.

What condition is associated with WDR45 p.Arg111fs (c.332_338del)?

WDR45 p.Arg111fs (c.332_338del) is associated with neurodegeneration with brain iron accumulation 5 (ClinVar).

How common is WDR45 p.Arg111fs (c.332_338del) in the general population?

WDR45 p.Arg111fs (c.332_338del) is absent from gnomAD (gnomAD).

WDR45 p.Arg111fs

Q: How is Beta-propeller protein-associated neurodegeneration inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.332_338del · rs2147816498 · VCV1070071

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neurodegeneration with brain iron accumulation 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 0.75, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: WDR45
Protein: p.Arg111fs
Coding: c.332_338del
MANE Select: NM_001029896
dbSNP: rs2147816498
Type: Deletion
Location: chrX:49076648 (GRCh38)
Structure: AlphaFold pLDDT 90.66 · 3 PDB
Residue 111: a UniProt-annotated variant site (in nbia5); a β-strand

Full WDR45 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodegeneration with brain iron accumulation 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Beta-propeller protein-associated neurodegeneration (Orphanet):

Inheritance: X-linked dominant
Onset: Childhood

Similar variants

WDR45 p.Arg111Cys Uncertain significance ★★ ⚠ same residue
WDR45 p.Arg111His Uncertain significance ★★ ⚠ same residue
WDR45 p.Arg111= Likely benign ★ same residue
WDR45 p.Ile195fs Pathogenic ★★ same condition
WDR45 p.Phe136fs Pathogenic/Likely pathogenic ★★ same condition
WDR45 p.Tyr124fs Pathogenic ★★ same condition
WDR45 c.827+12del Benign/Likely benign ★★ same condition
WDR45 c.974-9del Benign/Likely benign ★★ 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/wdr45-p-arg111fs (accessed [today's date]).

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