Is DEPDC5 p.Cys952= (c.2856T>C) pathogenic?

DEPDC5 p.Cys952= (c.2856T>C) is classified Benign/Likely benign in DEPDC5 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). Low-frequency (popmax 1.28%, afr); Associated with Inborn genetic diseases.

What condition is associated with DEPDC5 p.Cys952= (c.2856T>C)?

DEPDC5 p.Cys952= (c.2856T>C) is associated with Inborn genetic diseases, familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Cys952= (c.2856T>C) in the general population?

DEPDC5 p.Cys952= (c.2856T>C) is low-frequency (popmax 1.28%, afr) (gnomAD).

DEPDC5 p.Cys952=

c.2856T>C · rs115299174 · VCV414445

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.228	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -1.1
Overall
CADD	6.287	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% African / African-American · 960/75,064 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.0657% 1,060/1,614,190 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.28%	78
Remaining individualsnot grpmax-eligible	0.0656%	1,525
Admixed American	0.0633%	1,580
Middle Eastern	0.033%	3,030
South Asian	0.00768%	13,013
European (non-Finnish)	0.00102%	98,334

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.Cys952=
Coding: c.2856T>C
MANE Select: NM_001242896
dbSNP: rs115299174
Type: single nucleotide variant
Location: chr22:31845072 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial focal epilepsy with variable foci

Similar variants

DEPDC5 p.Cys952Ter Pathogenic ★ same residue
DEPDC5 c.1217+1G>A Likely pathogenic ★★ same condition
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-cys952 (accessed [today's date]).

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