Is WWOX p.Pro384Ser (c.1150C>T) pathogenic?

WWOX p.Pro384Ser (c.1150C>T) is classified Uncertain significance in WWOX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). AlphaMissense: ambiguous (0.3706); Ultra-rare (popmax 0.0156%, eas); Associated with autosomal recessive spinocerebellar ataxia 12.

What condition is associated with WWOX p.Pro384Ser (c.1150C>T)?

WWOX p.Pro384Ser (c.1150C>T) is associated with autosomal recessive spinocerebellar ataxia 12, developmental and epileptic encephalopathy, 1 (ClinVar).

How common is WWOX p.Pro384Ser (c.1150C>T) in the general population?

WWOX p.Pro384Ser (c.1150C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about WWOX p.Pro384Ser (c.1150C>T)?

AlphaMissense predicts ambiguous (score 0.3706) — an in-silico prediction, not a clinical call.

WWOX p.Pro384Ser

Q: How is Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1150C>T · rs544760115 · VCV661599

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

autosomal recessive spinocerebellar ataxia 12

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3706	ambiguous
REVEL	0.285	benign-leaning
SaProt	LLR -7.27	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 1.69	unconstrained · MANE · 1,112 kb · p 9.9e-59 · regional, not allelic
Overall
CADD	22.4	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 0.0156% East Asian · 7/44,866 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000496% 8/1,614,244 alleles · ultra-rare exomes 3/1,461,892 · genomes 5/152,352 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,409
European (non-Finnish)	8.47e-05%	1,180,050

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: WWOX
Protein: p.Pro384Ser
Coding: c.1150C>T
MANE Select: NM_016373
dbSNP: rs544760115
Type: single nucleotide variant
Location: chr16:79211701 (GRCh38)

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

Disease context

autosomal recessive spinocerebellar ataxia 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: developmental and epileptic encephalopathy, 1

For Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

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/wwox-p-pro384ser (accessed [today's date]).

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