Is WWOX p.Ala2= (c.6A>G) pathogenic?

WWOX p.Ala2= (c.6A>G) is classified Likely benign in WWOX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-22). Very rare (popmax 0.00199%, amr); Associated with developmental and epileptic encephalopathy, 1.

What condition is associated with WWOX p.Ala2= (c.6A>G)?

WWOX p.Ala2= (c.6A>G) is associated with developmental and epileptic encephalopathy, 1, autosomal recessive spinocerebellar ataxia 12 (ClinVar).

How common is WWOX p.Ala2= (c.6A>G) in the general population?

WWOX p.Ala2= (c.6A>G) is very rare (popmax 0.00199%, amr) (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.Ala2=

c.6A>G · VCV3749755

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00199%, amr)

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 0.67	GERP -4.2, phastCons 0.97
Overall
CADD	7.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00199% Admixed American · 1/50,190 alleles

Overall 0.000657% 1/152,194 alleles · very rare

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.Ala2=
Coding: c.6A>G
MANE Select: NM_016373
Type: single nucleotide variant
Location: chr16:78099784 (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 2: the 'disordered' region

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 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
WWOX c.791+1G>T Likely 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-ala2 (accessed [today's date]).

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