Is DCC p.Gln1193Arg (c.3578A>G) pathogenic?

DCC p.Gln1193Arg (c.3578A>G) is classified Likely benign in DCC (ClinVar, Single submitter, 2 submitters; last evaluated 2020-07-09). AlphaMissense: likely benign (0.1196); Ultra-rare (popmax 0.0691%, eas).

How common is DCC p.Gln1193Arg (c.3578A>G) in the general population?

DCC p.Gln1193Arg (c.3578A>G) is ultra-rare (popmax 0.0691%, eas) (gnomAD).

What do computational predictors say about DCC p.Gln1193Arg (c.3578A>G)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

DCC p.Gln1193Arg

c.3578A>G · rs375401214 · VCV2053266

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0691%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 0.72, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 1,190 kb · p 0.4 · regional, not allelic
Overall
CADD	23.5	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

Grpmax group 0.0691% East Asian · 31/44,860 alleles

Filtering AF 0.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0435%

Overall 0.00533% 86/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0691%	1,447
Remaining individualsnot grpmax-eligible	0.0464%	2,155
South Asian	0.0209%	4,794
African / African-American	0.00666%	15,010
European (non-Finnish)	0.00017%	589,953

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.Gln1193Arg
Coding: c.3578A>G
MANE Select: NM_005215
dbSNP: rs375401214
Type: single nucleotide variant
Location: chr18:53459417 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1193: 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

Similar variants

DCC p.Gln1193Ter Pathogenic ★ same residue
DCC p.Gln1193His Uncertain significance ★ ⚠ same residue
DCC p.Arg1021Ter Pathogenic ★★ same type
DCC p.Arg1025Ter Pathogenic/Likely pathogenic ★★ same type
DCC p.Arg275Ter Pathogenic ★★ same type
DCC p.Arg879Ter Pathogenic/Likely pathogenic ★★ same type
DCC c.3620-2A>G Uncertain significance ★★ same type
DCC p.Arg597Gln Uncertain significance ★★ ⚠ same type

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-gln1193arg (accessed [today's date]).

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