DCC p.Trp508Ter
c.1523G>A · VCV4939087
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
DCC-related disorder
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 LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 9 of 29 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 44.0 | 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
- DCC
- Protein
- p.Trp508Ter
- Coding
- c.1523G>A
- MANE Select
- NM_005215
- Type
- single nucleotide variant
- Location
- chr18:53179066 (GRCh38)
- Gene constraint
- LOEUF 0.414 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.60 · 9 PDB
- Residue 508
- a UniProt-annotated variant site (in mrmv1; likely pathogenic); a β-strand; the fibronectin type-iii 1 domain
Disease context
DCC-related disorder
Similar variants
- DCC c.2828-1G>A Likely pathogenic ★ same condition
- DCC c.3898+2T>C Likely pathogenic ★ same condition
- DCC p.Arg501Ter Likely pathogenic ★ same condition
- DCC p.Glu512Ter Likely pathogenic ★ same condition
- DCC p.Trp745Ter Likely pathogenic ★ same condition
- DCC p.Pro1086Leu Uncertain significance ⚠ same condition
- DCC p.Thr614Ile Uncertain significance ⚠ same condition
- DCC c.2360-4C>T Likely benign 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/dcc-p-trp508ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown