Is WDR45B p.Ile245Val (c.733A>G) pathogenic?

WDR45B p.Ile245Val (c.733A>G) is classified Conflicting classifications of pathogenicity in WDR45B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-24). AlphaMissense: likely benign (0.1065); Very rare (popmax 0.00102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WDR45B p.Ile245Val (c.733A>G)?

WDR45B p.Ile245Val (c.733A>G) is associated with Inborn genetic diseases (ClinVar).

How common is WDR45B p.Ile245Val (c.733A>G) in the general population?

WDR45B p.Ile245Val (c.733A>G) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about WDR45B p.Ile245Val (c.733A>G)?

AlphaMissense predicts likely benign (score 0.1065) — an in-silico prediction, not a clinical call.

WDR45B p.Ile245Val

c.733A>G · VCV4083958

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1065	likely benign
REVEL	0.215	benign-leaning
SaProt	LLR -6.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 32 kb · p 2.4e-07 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,180,014 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000743% 12/1,614,150 alleles · very rare exomes 12/1,461,844 · genomes 0/152,306 · joint denominator

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: WDR45B
Protein: p.Ile245Val
Coding: c.733A>G
MANE Select: NM_019613
Type: single nucleotide variant
Location: chr17:82617369 (GRCh38)
Gene constraint: LOEUF 0.634 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 94.78 · 5 PDB
Residue 245: a β-strand; a UniProt-annotated variant site (in nedsbas; uncertain significance)

Full WDR45B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WDR45B p.Ala192Val Uncertain significance ★ ⚠ same condition
WDR45B p.Ala334Thr Uncertain significance ★ ⚠ same condition
WDR45B p.Ala67Thr Uncertain significance ★ ⚠ same condition
WDR45B p.Arg108Gln Uncertain significance ★ ⚠ same condition
WDR45B p.Arg108Trp Uncertain significance ★ ⚠ same condition
WDR45B p.Arg34Gln Uncertain significance ★ ⚠ same condition
WDR45B p.Asn323Ser Uncertain significance ★ ⚠ same condition
WDR45B p.Asp250Asn Uncertain significance ★ 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/wdr45b-p-ile245val (accessed [today's date]).

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