Is DCC p.Arg1124Cys (c.3370C>T) pathogenic?

DCC p.Arg1124Cys (c.3370C>T) is classified Conflicting classifications of pathogenicity in DCC (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-01). AlphaMissense: ambiguous (0.5339); Rare (popmax 0.214%, mid); Associated with Inborn genetic diseases.

What condition is associated with DCC p.Arg1124Cys (c.3370C>T)?

DCC p.Arg1124Cys (c.3370C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCC p.Arg1124Cys (c.3370C>T) in the general population?

DCC p.Arg1124Cys (c.3370C>T) is rare (popmax 0.214%, mid) (gnomAD).

What do computational predictors say about DCC p.Arg1124Cys (c.3370C>T)?

AlphaMissense predicts ambiguous (score 0.5339) — an in-silico prediction, not a clinical call.

DCC p.Arg1124Cys

c.3370C>T · rs547920182 · VCV3080399

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5339 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.214%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5339	ambiguous
REVEL	0.533	indeterminate
SaProt	—	withheld · numbering disagrees past residue 178 · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.214% Middle Eastern · 13/6,062 alleles

Filtering AF 0.127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.101%

Overall 0.0138% 223/1,613,586 alleles · rare exomes 214/1,461,344 · genomes 9/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.214%	466
South Asian	0.0813%	1,231
Remaining individualsnot grpmax-eligible	0.0224%	4,463
European (non-Finnish)	0.00958%	10,439
Admixed American	0.005%	20,003
East Asian	0.00446%	22,433
Finnishnot grpmax-eligible	0.00313%	32,000
African / African-American	0.00267%	37,497

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DCC
Protein: p.Arg1124Cys
Coding: c.3370C>T
MANE Select: NM_005215
dbSNP: rs547920182
Type: single nucleotide variant
Location: chr18:53450640 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1124: 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.Arg215Ter Pathogenic ★ same condition
DCC c.3392+4G>A Uncertain significance ★ same condition
DCC c.986-3C>T Uncertain significance ★ 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-arg1124cys (accessed [today's date]).

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