Is WNT9B p.Arg63Gln (c.188G>A) pathogenic?

WNT9B p.Arg63Gln (c.188G>A) is classified Uncertain significance in WNT9B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-23). AlphaMissense: likely benign (0.1373); Ultra-rare (popmax 0.0267%, eas); Associated with Inborn genetic diseases.

What condition is associated with WNT9B p.Arg63Gln (c.188G>A)?

WNT9B p.Arg63Gln (c.188G>A) is associated with Inborn genetic diseases (ClinVar).

How common is WNT9B p.Arg63Gln (c.188G>A) in the general population?

WNT9B p.Arg63Gln (c.188G>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about WNT9B p.Arg63Gln (c.188G>A)?

AlphaMissense predicts likely benign (score 0.1373) — an in-silico prediction, not a clinical call.

WNT9B p.Arg63Gln

c.188G>A · rs149418183 · VCV2908065

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1373 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1373	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -9.21	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 6.1	GERP 3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 25 kb · p 0.05 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0267% East Asian · 12/44,880 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00242% 39/1,613,396 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,740
African / African-American	0.02%	4,995
Admixed American	0.005%	19,991
South Asian	0.0033%	30,330
Remaining individualsnot grpmax-eligible	0.0032%	31,228
European (non-Finnish)	0.000339%	294,980

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: WNT9B
Protein: p.Arg63Gln
Coding: c.188G>A
MANE Select: NM_001006607 · reported on NM_003396
dbSNP: rs149418183
Type: single nucleotide variant
Location: chr17:46872627 (GRCh38)

Full WNT9B 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

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/wnt9b-p-arg63gln (accessed [today's date]).

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