Is WDR45 p.Pro339= (c.1017T>C) pathogenic?

WDR45 p.Pro339= (c.1017T>C) is classified Likely benign in WDR45 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Absent from gnomAD v4.1; Associated with neurodegeneration with brain iron accumulation 5.

What condition is associated with WDR45 p.Pro339= (c.1017T>C)?

WDR45 p.Pro339= (c.1017T>C) is associated with neurodegeneration with brain iron accumulation 5 (ClinVar).

How common is WDR45 p.Pro339= (c.1017T>C) in the general population?

WDR45 p.Pro339= (c.1017T>C) is absent from gnomAD v4.1 (gnomAD).

WDR45 p.Pro339=

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.1017T>C · rs2520259055 · VCV2814101

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

neurodegeneration with brain iron accumulation 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.68 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.65	GERP -3.7
Overall
CADD	4.813	PHRED · no single calibrated threshold — expert panels disagree

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: WDR45
Protein: p.Pro339=
Coding: c.1017T>C
MANE Select: NM_001029896
dbSNP: rs2520259055
Type: single nucleotide variant
Location: chrX:49074869 (GRCh38)
Structure: AlphaFold pLDDT 90.66 · 3 PDB
Residue 339: a UniProt-annotated variant site (in nbia5)

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.Pro339fs Pathogenic ★ same residue
WDR45 c.342-2A>G Pathogenic/Likely pathogenic ★★ same condition
WDR45 c.342-3C>G Pathogenic/Likely pathogenic ★★ same condition
WDR45 c.437-1G>A Pathogenic/Likely pathogenic ★★ same condition
WDR45 c.437-2A>G Pathogenic ★★ same condition
WDR45 c.516+1G>A Pathogenic ★★ same condition
WDR45 c.726-1G>A Pathogenic ★★ same condition
WDR45 c.726-2A>G 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/wdr45-p-pro339 (accessed [today's date]).

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