Is DEPDC5 p.Arg1007= (c.3021G>T) pathogenic?

DEPDC5 p.Arg1007= (c.3021G>T) is classified Conflicting classifications of pathogenicity in DEPDC5 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0436%, nfe); Associated with familial focal epilepsy with variable foci.

What condition is associated with DEPDC5 p.Arg1007= (c.3021G>T)?

DEPDC5 p.Arg1007= (c.3021G>T) is associated with familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Arg1007= (c.3021G>T) in the general population?

DEPDC5 p.Arg1007= (c.3021G>T) is ultra-rare (popmax 0.0436%, 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.Arg1007=

c.3021G>T · rs201690337 · VCV580999

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0436%, 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 · G>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 0.61, phastCons 1
Overall
CADD	18.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0436% European (non-Finnish) · 514/1,179,402 alleles

Filtering AF 0.0404% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.0353% 569/1,612,598 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0641%	1,561
European (non-Finnish)grpmax	0.0436%	2,295
African / African-American	0.0133%	7,493
Admixed American	0.00669%	14,948
South Asian	0.0011%	90,818

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg1007=
Coding: c.3021G>T
MANE Select: NM_001242896
dbSNP: rs201690337
Type: single nucleotide variant
Location: chr22:31845237 (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.Arg1007Trp Uncertain significance ★★ ⚠ same residue
DEPDC5 p.Arg1007Gln 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
DEPDC5 c.2105-1G>A 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-arg1007 (accessed [today's date]).

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