Is DEPDC5 p.Arg243Gln (c.728G>A) pathogenic?

DEPDC5 p.Arg243Gln (c.728G>A) is classified Uncertain significance in DEPDC5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0572); Very rare (popmax 0.00138%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DEPDC5 p.Arg243Gln (c.728G>A)?

DEPDC5 p.Arg243Gln (c.728G>A) is associated with Inborn genetic diseases, familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Arg243Gln (c.728G>A) in the general population?

DEPDC5 p.Arg243Gln (c.728G>A) is very rare (popmax 0.00138%, nfe) (gnomAD).

What do computational predictors say about DEPDC5 p.Arg243Gln (c.728G>A)?

AlphaMissense predicts likely benign (score 0.0572) — an in-silico prediction, not a clinical call.

DEPDC5 p.Arg243Gln

c.728G>A · rs368129922 · VCV1052213

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00138%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0572	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -3.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 3.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 64 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00138% European (non-Finnish) · 16/1,158,876 alleles

Filtering AF 0.000817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000661%

Overall 0.00103% 16/1,552,606 alleles · very rare

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.Arg243Gln
Coding: c.728G>A
MANE Select: NM_001242896
dbSNP: rs368129922
Type: single nucleotide variant
Location: chr22:31792778 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB
Residue 243: 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.Arg243Ter Pathogenic ★★ same residue
DEPDC5 p.Arg243Leu 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

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-arg243gln (accessed [today's date]).

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