Is WDR45 p.Asp83= (c.249C>T) pathogenic?

WDR45 p.Asp83= (c.249C>T) is classified Benign in WDR45 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Ultra-rare (popmax 0.0251%, sas); Associated with neurodegeneration with brain iron accumulation 5.

What condition is associated with WDR45 p.Asp83= (c.249C>T)?

WDR45 p.Asp83= (c.249C>T) is associated with neurodegeneration with brain iron accumulation 5 (ClinVar).

How common is WDR45 p.Asp83= (c.249C>T) in the general population?

WDR45 p.Asp83= (c.249C>T) is ultra-rare (popmax 0.0251%, sas) (gnomAD).

WDR45 p.Asp83=

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.249C>T · rs782706648 · VCV1168755

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0251%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.59	GERP -3.5
Overall
CADD	2.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0251% South Asian · 14/55,819 alleles

Filtering AF 0.0151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0015% 18/1,203,424 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0251%	3,987
Admixed American	0.00222%	44,967
European (non-Finnish)	0.000337%	297,157

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: WDR45
Protein: p.Asp83=
Coding: c.249C>T
MANE Select: NM_001029896
dbSNP: rs782706648
Type: single nucleotide variant
Location: chrX:49076737 (GRCh38)
Structure: AlphaFold pLDDT 90.66 · 3 PDB
Residue 83: 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.Asp83Tyr Uncertain significance ★ ⚠ 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-asp83 (accessed [today's date]).

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