Is DEPDC5 p.Gln1069Ter (c.3205C>T) pathogenic?

DEPDC5 p.Gln1069Ter (c.3205C>T) is classified Pathogenic in DEPDC5 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-18). Absent from gnomAD v4.1; Associated with familial focal epilepsy with variable foci.

What condition is associated with DEPDC5 p.Gln1069Ter (c.3205C>T)?

DEPDC5 p.Gln1069Ter (c.3205C>T) is associated with familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Gln1069Ter (c.3205C>T) in the general population?

DEPDC5 p.Gln1069Ter (c.3205C>T) is absent from gnomAD v4.1 (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.Gln1069Ter

c.3205C>T · rs2149117486 · VCV1069404

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

familial focal epilepsy with variable foci

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 32 of 43
REVEL	0.076	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 4.6, phastCons 0.99
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DEPDC5
Protein: p.Gln1069Ter
Coding: c.3205C>T
MANE Select: NM_001242896
dbSNP: rs2149117486
Type: single nucleotide variant
Location: chr22:31857494 (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.Gln1069Pro Uncertain significance ★★ ⚠ same residue
DEPDC5 p.Gln1069Arg Uncertain significance ★ ⚠ same residue
DEPDC5 p.Gln1069His Uncertain significance ★ ⚠ same residue
DEPDC5 c.1218-1G>A Pathogenic ★★ same condition
DEPDC5 c.1287+1G>A Pathogenic/Likely pathogenic ★★ same condition
DEPDC5 c.1324+1G>A Likely pathogenic ★★ same condition
DEPDC5 c.1324+1G>T Likely pathogenic ★★ same condition
DEPDC5 c.193+1G>T Pathogenic/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/depdc5-p-gln1069ter (accessed [today's date]).

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