Is DEPDC5 p.Pro430= (c.1290C>T) pathogenic?

DEPDC5 p.Pro430= (c.1290C>T) is classified Likely benign in DEPDC5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-23). Ultra-rare (popmax 0.0681%, nfe); Associated with familial focal epilepsy with variable foci.

What condition is associated with DEPDC5 p.Pro430= (c.1290C>T)?

DEPDC5 p.Pro430= (c.1290C>T) is associated with familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Pro430= (c.1290C>T) in the general population?

DEPDC5 p.Pro430= (c.1290C>T) is ultra-rare (popmax 0.0681%, 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.Pro430=

c.1290C>T · rs201202102 · VCV444584

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, 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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.002	GERP 1.4, phastCons 0.95
Overall
CADD	13.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0681% European (non-Finnish) · 804/1,179,842 alleles

Filtering AF 0.0642% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0626%

Overall 0.0521% 840/1,613,692 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0681%	1,467
Remaining individualsnot grpmax-eligible	0.032%	3,124
Middle Eastern	0.0164%	6,082
African / African-American	0.012%	8,320
Admixed American	0.00834%	11,992
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594

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.Pro430=
Coding: c.1290C>T
MANE Select: NM_001242896
dbSNP: rs201202102
Type: single nucleotide variant
Location: chr22:31809613 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB
Residue 430: the 'disordered' region

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-pro430 (accessed [today's date]).

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