Is DEPDC5 p.Phe30fs (c.88_89insA) pathogenic?

DEPDC5 p.Phe30fs (c.8889insA) is classified Likely pathogenic in DEPDC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). Absent from gnomAD; Associated with epilepsy, familial focal, with variable foci 1.

What condition is associated with DEPDC5 p.Phe30fs (c.88_89insA)?

DEPDC5 p.Phe30fs (c.88_89insA) is associated with epilepsy, familial focal, with variable foci 1 (ClinVar).

How common is DEPDC5 p.Phe30fs (c.88_89insA) in the general population?

DEPDC5 p.Phe30fs (c.88_89insA) is absent from gnomAD (gnomAD).

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.Phe30fs

c.88_89insA · rs2517738978 · VCV2671635

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 4.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DEPDC5
Protein: p.Phe30fs
Coding: c.88_89insA
MANE Select: NM_001242896
dbSNP: rs2517738978
Type: Insertion
Location: chr22:31758575 (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.Phe30Leu Uncertain significance ★★ ⚠ same residue
DEPDC5 p.Ser1085fs Pathogenic ★ same condition
DEPDC5 p.Phe30Tyr Uncertain significance ★ ⚠ same residue
DEPDC5 c.1287+1G>A Pathogenic/Likely pathogenic ★★ same condition
DEPDC5 c.1324+1G>T Likely pathogenic ★★ same condition
DEPDC5 c.3021+1G>A Pathogenic ★★ same condition
DEPDC5 c.413+1G>A Pathogenic/Likely pathogenic ★★ same condition
DEPDC5 c.562+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/depdc5-p-phe30fs (accessed [today's date]).

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