Is WDR45 p.Val172= (c.516G>A) pathogenic?

WDR45 p.Val172= (c.516G>A) is classified Conflicting classifications of pathogenicity in WDR45 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-02-03). Absent from gnomAD v4.1; Associated with WDR45-related disorder.

What condition is associated with WDR45 p.Val172= (c.516G>A)?

WDR45 p.Val172= (c.516G>A) is associated with WDR45-related disorder, neurodegeneration with brain iron accumulation 5 (ClinVar).

How common is WDR45 p.Val172= (c.516G>A) in the general population?

WDR45 p.Val172= (c.516G>A) is absent from gnomAD v4.1 (gnomAD).

WDR45 p.Val172=

c.516G>A · rs387907330 · VCV2092216

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

WDR45-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.193	benign-leaning
Splicing
SpliceAI	Δ0.84	donor loss · deltas
Pangolin	Δ0.66	loss · gain 0.28 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Overall
CADD	28.5	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.Val172=
Coding: c.516G>A
MANE Select: NM_001029896
dbSNP: rs387907330
Type: single nucleotide variant
Location: chrX:49075866 (GRCh38)
Structure: AlphaFold pLDDT 90.66 · 3 PDB
Residue 172: 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

WDR45-related disorder

Also linked: neurodegeneration with brain iron accumulation 5

Similar variants

WDR45 p.Val172Met 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-val172 (accessed [today's date]).

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