Is DCC p.Arg597Pro (c.1790G>C) pathogenic?

DCC p.Arg597Pro (c.1790G>C) is classified Pathogenic in DCC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-01-01). AlphaMissense: likely pathogenic (0.9973); Absent from gnomAD v4.1; Associated with corpus callosum, agenesis of.

What condition is associated with DCC p.Arg597Pro (c.1790G>C)?

DCC p.Arg597Pro (c.1790G>C) is associated with corpus callosum, agenesis of (ClinVar).

How common is DCC p.Arg597Pro (c.1790G>C) in the general population?

DCC p.Arg597Pro (c.1790G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCC p.Arg597Pro (c.1790G>C)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

DCC p.Arg597Pro

c.1790G>C · rs1057519056 · VCV375284

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

corpus callosum, agenesis of

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic ✓ concordant with ClinVar · top 1% in DCC
REVEL	0.771	pathogenic-leaning
SaProt	LLR -16.42	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	29.6	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

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.Arg597Pro
Coding: c.1790G>C
MANE Select: NM_005215
dbSNP: rs1057519056
Type: single nucleotide variant
Location: chr18:53207746 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 597: the fibronectin type-iii 2 domain; a UniProt-annotated variant site (in mrmv1; likely pathogenic); a UniProt-annotated variant site (in mrmv1; uncertain significance); a β-strand

Full DCC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

corpus callosum, agenesis of — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCC p.Arg597Gln Uncertain significance ★★ ⚠ same residue
DCC p.Arg597Ter Pathogenic ★ same residue
DCC p.Arg275Ter Pathogenic ★★ same condition
DCC p.Met743Leu Uncertain significance ★ ⚠ same condition
DCC p.Val754Met Uncertain significance ★ ⚠ same condition
DCC p.Ala893Thr Pathogenic ⚠ same condition
DCC p.Gly805Glu Pathogenic same condition
DCC p.Val793Gly 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-arg597pro (accessed [today's date]).

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