Is DEPDC5 p.Asn613Ser (c.1838A>G) pathogenic?

DEPDC5 p.Asn613Ser (c.1838A>G) is classified Conflicting classifications of pathogenicity in DEPDC5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-04-04). AlphaMissense: likely pathogenic (0.706); Absent from gnomAD v4.1; Associated with familial focal epilepsy with variable foci.

What condition is associated with DEPDC5 p.Asn613Ser (c.1838A>G)?

DEPDC5 p.Asn613Ser (c.1838A>G) is associated with familial focal epilepsy with variable foci, focal epilepsy, epilepsy, familial focal, with variable foci 1 (ClinVar).

How common is DEPDC5 p.Asn613Ser (c.1838A>G) in the general population?

DEPDC5 p.Asn613Ser (c.1838A>G) 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.

What do computational predictors say about DEPDC5 p.Asn613Ser (c.1838A>G)?

AlphaMissense predicts likely pathogenic (score 0.706) — an in-silico prediction, not a clinical call.

DEPDC5 p.Asn613Ser

c.1838A>G · rs2089445867 · VCV1507278

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.706 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial focal epilepsy with variable foci

Computational evidence

Protein change
AlphaMissense	0.706	likely pathogenic
REVEL	0.288	benign-leaning
SaProt	LLR -4.74	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4.1, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 2,336 bp · p 0.00015 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Asn613Ser
Coding: c.1838A>G
MANE Select: NM_001242896
dbSNP: rs2089445867
Type: single nucleotide variant
Location: chr22:31819193 (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

Also linked: focal epilepsy epilepsy, familial focal, with variable foci 1

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-asn613ser (accessed [today's date]).

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