Is DEPDC5 p.Phe682del (c.2043CTT[1]) pathogenic?

DEPDC5 p.Phe682del (c.2043CTT[1]) is classified Uncertain significance in DEPDC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-04). Very rare (popmax 0.000169%, nfe); Associated with familial focal epilepsy with variable foci.

What condition is associated with DEPDC5 p.Phe682del (c.2043CTT[1])?

DEPDC5 p.Phe682del (c.2043CTT[1]) is associated with familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Phe682del (c.2043CTT[1]) in the general population?

DEPDC5 p.Phe682del (c.2043CTT[1]) is very rare (popmax 0.000169%, nfe) (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.Phe682del

c.2043CTT[1] · VCV3680159

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

familial focal epilepsy with variable foci

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 3.7, phastCons 1
Overall
CADD	16.45	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,992 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: DEPDC5
Protein: p.Phe682del
Coding: c.2043CTT[1]
MANE Select: NM_001242896
Type: Microsatellite
Location: chr22:31822729 (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

familial focal epilepsy with variable foci — 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.Phe682Tyr Uncertain significance ★★ ⚠ same residue
DEPDC5 p.His490fs Pathogenic/Likely pathogenic ★★ same condition
DEPDC5 p.Ser655fs Pathogenic ★★ same condition
DEPDC5 p.Val73fs Pathogenic/Likely pathogenic ★★ same condition
DEPDC5 p.Gln1058del Uncertain significance ★★ same condition
DEPDC5 c.1218-13_1218-10del Benign/Likely benign ★★ same condition
DEPDC5 c.562+8_562+9del Benign/Likely benign ★★ same condition
DEPDC5 p.Arg263fs 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-phe682del (accessed [today's date]).

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