Is DEPDC5 p.Phe234fs (c.699dup) pathogenic?

DEPDC5 p.Phe234fs (c.699dup) is classified Likely pathogenic in DEPDC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). Associated with epilepsy, familial focal, with variable foci 1.

What condition is associated with DEPDC5 p.Phe234fs (c.699dup)?

DEPDC5 p.Phe234fs (c.699dup) is associated with epilepsy, familial focal, with variable foci 1 (ClinVar).

How is Familial focal epilepsy with variable foci inherited?

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

DEPDC5 p.Phe234fs

c.699dup · VCV3370499

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

epilepsy, familial focal, with variable foci 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 12 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 4.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DEPDC5
Protein: p.Phe234fs
Coding: c.699dup
MANE Select: NM_001242896
Type: Duplication
Location: chr22:31792747 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB

Full DEPDC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, familial focal, with variable foci 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial focal epilepsy with variable foci (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

DEPDC5 p.Ile67fs Pathogenic ★★ same condition
DEPDC5 p.Arg1363fs Likely pathogenic ★ same condition
DEPDC5 p.Glu900fs Likely pathogenic ★ same condition
DEPDC5 p.His576fs Likely pathogenic ★ same condition
DEPDC5 p.Met1017fs Likely pathogenic ★ same condition
DEPDC5 p.Val1419fs Likely pathogenic ★ same condition
DEPDC5 p.Val146fs Likely pathogenic ★ same condition
DEPDC5 c.(146+1_147-1 Uncertain significance ★ 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/depdc5-p-phe234fs (accessed [today's date]).

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