Is DEPDC5 p.Ser168= (c.504G>A) pathogenic?

DEPDC5 p.Ser168= (c.504G>A) is classified Conflicting classifications of pathogenicity in DEPDC5 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00334%, amr); Associated with Inborn genetic diseases.

What condition is associated with DEPDC5 p.Ser168= (c.504G>A)?

DEPDC5 p.Ser168= (c.504G>A) is associated with Inborn genetic diseases, familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Ser168= (c.504G>A) in the general population?

DEPDC5 p.Ser168= (c.504G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

DEPDC5 p.Ser168=

c.504G>A · rs577652236 · VCV859700

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2	GERP -7.9
Overall
CADD	4.584	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00334% Admixed American · 2/59,928 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00248% 40/1,613,432 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,964
European (non-Finnish)	0.00297%	33,706
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00133%	74,940
South Asian	0.0011%	91,006

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.Ser168=
Coding: c.504G>A
MANE Select: NM_001242896
dbSNP: rs577652236
Type: single nucleotide variant
Location: chr22:31783927 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB
Residue 168: a β-strand

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.Ser168Leu Uncertain significance ★★ ⚠ 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-ser168 (accessed [today's date]).

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