Is WDR45 p.Phe161Ser (c.482T>C) pathogenic?

WDR45 p.Phe161Ser (c.482T>C) is classified Uncertain significance in WDR45 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-21). AlphaMissense: likely pathogenic (0.9951); Absent from gnomAD v4.1; Associated with neurodegeneration with brain iron accumulation 5.

What condition is associated with WDR45 p.Phe161Ser (c.482T>C)?

WDR45 p.Phe161Ser (c.482T>C) is associated with neurodegeneration with brain iron accumulation 5 (ClinVar).

How common is WDR45 p.Phe161Ser (c.482T>C) in the general population?

WDR45 p.Phe161Ser (c.482T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about WDR45 p.Phe161Ser (c.482T>C)?

AlphaMissense predicts likely pathogenic (score 0.9951) — an in-silico prediction, not a clinical call.

WDR45 p.Phe161Ser

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.482T>C · rs2147815698 · VCV1493646

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9951 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

neurodegeneration with brain iron accumulation 5

Computational evidence

Protein change
AlphaMissense	0.9951	likely pathogenic
REVEL	0.53	indeterminate
SaProt	LLR -11.91	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.44, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 2,402 bp · p 8.3e-07 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Phe161Ser
Coding: c.482T>C
MANE Select: NM_001029896
dbSNP: rs2147815698
Type: single nucleotide variant
Location: chrX:49075900 (GRCh38)
Structure: AlphaFold pLDDT 90.66 · 3 PDB
Residue 161: 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-phe161ser (accessed [today's date]).

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