Is DEPDC5 p.Pro338= (c.1014C>T) pathogenic?

DEPDC5 p.Pro338= (c.1014C>T) is classified Likely benign in DEPDC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0205%, amr); Associated with familial focal epilepsy with variable foci.

What condition is associated with DEPDC5 p.Pro338= (c.1014C>T)?

DEPDC5 p.Pro338= (c.1014C>T) is associated with familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Pro338= (c.1014C>T) in the general population?

DEPDC5 p.Pro338= (c.1014C>T) is ultra-rare (popmax 0.0205%, amr) (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.Pro338=

c.1014C>T · rs774034064 · VCV414469

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0205%, amr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -8.1
Overall
CADD	2.232	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0205% Admixed American · 12/58,400 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00921%

Overall 0.00138% 20/1,453,550 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0205%	4,867
Middle Eastern	0.0165%	6,048
East Asian	0.00226%	44,236
South Asian	0.00224%	44,600
European (non-Finnish)	0.00034%	294,126

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.Pro338=
Coding: c.1014C>T
MANE Select: NM_001242896
dbSNP: rs774034064
Type: single nucleotide variant
Location: chr22:31802771 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB
Residue 338: a β-strand

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 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
DEPDC5 c.2105-1G>A Likely pathogenic ★★ same condition
DEPDC5 c.2634-2A>G Likely pathogenic ★★ same condition
DEPDC5 c.280-1G>A 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-pro338 (accessed [today's date]).

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