Is DEPDC5 p.Phe250Val (c.748T>G) pathogenic?

DEPDC5 p.Phe250Val (c.748T>G) is classified Likely benign in DEPDC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). AlphaMissense: likely pathogenic (0.741); Rare (popmax 0.105%, afr); Associated with Inborn genetic diseases.

What condition is associated with DEPDC5 p.Phe250Val (c.748T>G)?

DEPDC5 p.Phe250Val (c.748T>G) is associated with Inborn genetic diseases, familial focal epilepsy with variable foci (ClinVar).

How common is DEPDC5 p.Phe250Val (c.748T>G) in the general population?

DEPDC5 p.Phe250Val (c.748T>G) is rare (popmax 0.105%, afr) (gnomAD).

What do computational predictors say about DEPDC5 p.Phe250Val (c.748T>G)?

AlphaMissense predicts likely pathogenic (score 0.741) — an in-silico prediction, not a clinical call.

DEPDC5 p.Phe250Val

c.748T>G · rs201429774 · VCV699043

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.741 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.741	likely pathogenic
REVEL	0.237	benign-leaning
SaProt	LLR -13.61	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 4.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 64 kb · p 1.2e-06 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.105% African / African-American · 73/69,658 alleles

Filtering AF 0.0854% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0784%

Overall 0.00565% 87/1,541,140 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.105%	954
Remaining individualsnot grpmax-eligible	0.0135%	7,427
East Asian	0.0101%	9,929
Admixed American	0.00472%	21,170

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.Phe250Val
Coding: c.748T>G
MANE Select: NM_001242896
dbSNP: rs201429774
Type: single nucleotide variant
Location: chr22:31792798 (GRCh38)
Gene constraint: LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.22 · 11 PDB
Residue 250: 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.Phe250Leu 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-phe250val (accessed [today's date]).

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