Is WWOX p.Pro98= (c.294G>A) pathogenic?

WWOX p.Pro98= (c.294G>A) is classified Likely benign in WWOX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-18). Very rare (popmax 0.000254%, nfe); Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with WWOX p.Pro98= (c.294G>A)?

WWOX p.Pro98= (c.294G>A) is associated with developmental and epileptic encephalopathy, 1, autosomal recessive spinocerebellar ataxia 12 (ClinVar).

How common is WWOX p.Pro98= (c.294G>A) in the general population?

WWOX p.Pro98= (c.294G>A) is very rare (popmax 0.000254%, 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.Pro98=

c.294G>A · rs200208343 · VCV2008319

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

developmental and epileptic encephalopathy, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.7	GERP -4.1
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,018 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,138 alleles · very rare exomes 4/1,461,874 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	0.000254%	393,340

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.Pro98=
Coding: c.294G>A
MANE Select: NM_016373
dbSNP: rs200208343
Type: single nucleotide variant
Location: chr16:78115039 (GRCh38)
Gene constraint: LOEUF 1.82 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.43 · 1 PDB
Residue 98: a UniProt-annotated variant site (in)

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

Similar variants

WWOX p.Pro98Leu Benign/Likely benign ★★ same residue
WWOX c.107+1G>A Pathogenic/Likely pathogenic ★★ same condition
WWOX c.173-1G>C Pathogenic ★★ same condition
WWOX c.173-1G>T Pathogenic ★★ same condition
WWOX c.409+1G>C Pathogenic/Likely pathogenic ★★ same condition
WWOX c.410-1G>A Pathogenic/Likely pathogenic ★★ same condition
WWOX c.605+2T>C Pathogenic/Likely pathogenic ★★ same condition
WWOX c.606-1G>A 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/wwox-p-pro98 (accessed [today's date]).

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