Is WWOX p.Pro384= (c.1152C>G) pathogenic?

WWOX p.Pro384= (c.1152C>G) is classified Conflicting classifications of pathogenicity in WWOX (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-06-01). Very rare (popmax 8.47e-05%, nfe); Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with WWOX p.Pro384= (c.1152C>G)?

WWOX p.Pro384= (c.1152C>G) is associated with developmental and epileptic encephalopathy, 1, autosomal recessive spinocerebellar ataxia 12 (ClinVar).

How common is WWOX p.Pro384= (c.1152C>G) in the general population?

WWOX p.Pro384= (c.1152C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Infantile epileptic spasms syndrome inherited?

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

WWOX p.Pro384=

c.1152C>G · rs2051759603 · VCV1336332

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

developmental and epileptic encephalopathy, 1

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.1	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.2	GERP -1.6
Overall
CADD	1.342	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,048 alleles

Overall 0.000124% 2/1,614,232 alleles · very rare exomes 2/1,461,892 · genomes 0/152,340 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	8.47e-05%	1,180,048

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro384=
Coding: c.1152C>G
MANE Select: NM_016373
dbSNP: rs2051759603
Type: single nucleotide variant
Location: chr16:79211703 (GRCh38)

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

Disease context

developmental and epileptic encephalopathy, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive spinocerebellar ataxia 12

For Infantile epileptic spasms syndrome (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked dominant

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-pro384 (accessed [today's date]).

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