Is WDR45 p.Ser322= (c.966T>A) pathogenic?

WDR45 p.Ser322= (c.966T>A) is classified Likely benign in WDR45 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-13). Very rare (popmax 0.00694%, afr); Associated with neurodegeneration with brain iron accumulation 5.

What condition is associated with WDR45 p.Ser322= (c.966T>A)?

WDR45 p.Ser322= (c.966T>A) is associated with neurodegeneration with brain iron accumulation 5 (ClinVar).

How common is WDR45 p.Ser322= (c.966T>A) in the general population?

WDR45 p.Ser322= (c.966T>A) is very rare (popmax 0.00694%, afr) (gnomAD).

WDR45 p.Ser322=

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.966T>A · rs782034367 · VCV754855

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00694%, afr)

Conditions

neurodegeneration with brain iron accumulation 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.026	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 1.6, phastCons 1
Overall
CADD	8.864	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00694% African / African-American · 4/57,612 alleles

Filtering AF 0.00232% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00139%

Overall 0.000413% 5/1,210,341 alleles · very rare exomes 4/1,097,105 · genomes 1/113,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00694%	14,403
Admixed American	0.00217%	45,993

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.Ser322=
Coding: c.966T>A
MANE Select: NM_001029896
dbSNP: rs782034367
Type: single nucleotide variant
Location: chrX:49075143 (GRCh38)
Structure: AlphaFold pLDDT 90.66 · 3 PDB
Residue 322: 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 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
WDR45 c.827+1G>A 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-ser322 (accessed [today's date]).

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