Is DCC p.Pro1315fs (c.3944del) pathogenic?

DCC p.Pro1315fs (c.3944del) is classified Pathogenic in DCC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-25). Associated with gaze palsy, familial horizontal, with progressive scoliosis, 2.

What condition is associated with DCC p.Pro1315fs (c.3944del)?

DCC p.Pro1315fs (c.3944del) is associated with gaze palsy, familial horizontal, with progressive scoliosis, 2 (ClinVar).

DCC p.Pro1315fs

Q: How is Horizontal gaze palsy with progressive scoliosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.3944del · VCV4850760

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

gaze palsy, familial horizontal, with progressive scoliosis, 2

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 27 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 1

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

Variant & gene context

Gene: DCC
Protein: p.Pro1315fs
Coding: c.3944del
MANE Select: NM_005215
Type: Deletion
Location: chr18:53499339 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1315: the 'disordered' region; 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

gaze palsy, familial horizontal, with progressive scoliosis, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Horizontal gaze palsy with progressive scoliosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood

Similar variants

DCC p.Val263fs Pathogenic ★ same condition
DCC p.Pro1315Ala Uncertain significance ★ ⚠ same residue
DCC c.31_91+7622del Pathogenic same condition
DCC c.2053+13A>G Benign ★★ same condition
DCC c.2053+9T>C Benign/Likely benign ★★ same condition
DCC c.3130+10A>G Benign ★★ same condition
DCC c.91+7G>A Benign ★★ same condition
DCC p.Arg201Gly 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-pro1315fs (accessed [today's date]).

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