Is WWOX p.Pro386= (c.1158A>G) pathogenic?

WWOX p.Pro386= (c.1158A>G) is classified Likely benign in WWOX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). Very rare (popmax 0.00439%, sas); Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with WWOX p.Pro386= (c.1158A>G)?

WWOX p.Pro386= (c.1158A>G) is associated with developmental and epileptic encephalopathy, 1, autosomal recessive spinocerebellar ataxia 12 (ClinVar).

How common is WWOX p.Pro386= (c.1158A>G) in the general population?

WWOX p.Pro386= (c.1158A>G) is very rare (popmax 0.00439%, sas) (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.Pro386=

c.1158A>G · rs755586346 · VCV415949

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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	0.029	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -9.9	GERP -3.7
Overall
CADD	0.019	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,092 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00142% 23/1,614,228 alleles · very rare exomes 23/1,461,892 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,773
Remaining individualsnot grpmax-eligible	0.0032%	31,256
European (non-Finnish)	0.00144%	69,415

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.Pro386=
Coding: c.1158A>G
MANE Select: NM_016373
dbSNP: rs755586346
Type: single nucleotide variant
Location: chr16:79211709 (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-pro386 (accessed [today's date]).

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