DEPDC5 p.Trp1466Ter
c.4398G>A · rs2149419668 · VCV1364022
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
isolated focal cortical dysplasia type IIb
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | predicted | premature termination codon in exon 41 of 43 |
| REVEL | 0.783 | moderately pathogenic-leaning |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.8 | GERP 4.1, phastCons 1 |
| Overall | ||
| CADD | 42.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Trp1466Ter
- Coding
- c.4398G>A
- MANE Select
- NM_001242896
- dbSNP
- rs2149419668
- Type
- single nucleotide variant
- Location
- chr22:31901764 (GRCh38)
- Gene constraint
- LOEUF 0.403 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 65.22 · 11 PDB
- Residue 1466
- an α-helix
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-trp1466ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown