Is DCC p.Leu786fs (c.2353_2354dup) pathogenic?

DCC p.Leu786fs (c.23532354dup) is classified Pathogenic in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-19). Associated with Inborn genetic diseases.

What condition is associated with DCC p.Leu786fs (c.2353_2354dup)?

DCC p.Leu786fs (c.2353_2354dup) is associated with Inborn genetic diseases (ClinVar).

DCC p.Leu786fs

c.2353_2354dup · VCV4832987

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 15 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -5.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DCC
Protein: p.Leu786fs
Coding: c.2353_2354dup
MANE Select: NM_005215
Type: Microsatellite
Location: chr18:53339897 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 786: the fibronectin type-iii 4 domain; a UniProt-annotated variant site (in mrmv1; likely pathogenic)

Full DCC 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

Similar variants

DCC p.Arg1021Ter Pathogenic ★★ same condition
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same condition
DCC p.Gly84Arg Uncertain significance ★★ ⚠ same condition
DCC p.Ile1080Val Uncertain significance ★★ ⚠ same condition
DCC p.Gln486Leu Benign ★★ same condition
DCC p.Ala713fs Pathogenic ★ same condition
DCC p.Arg215Ter Pathogenic ★ same condition
DCC p.Pro847fs 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/dcc-p-leu786fs (accessed [today's date]).

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