Is DCC p.Ser1223= (c.3669G>A) pathogenic?

DCC p.Ser1223= (c.3669G>A) is classified Likely benign in DCC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-07). Ultra-rare (popmax 0.0767%, amr); Associated with DCC-related disorder.

What condition is associated with DCC p.Ser1223= (c.3669G>A)?

DCC p.Ser1223= (c.3669G>A) is associated with DCC-related disorder (ClinVar).

How common is DCC p.Ser1223= (c.3669G>A) in the general population?

DCC p.Ser1223= (c.3669G>A) is ultra-rare (popmax 0.0767%, amr) (gnomAD).

DCC p.Ser1223=

c.3669G>A · rs200234919 · VCV3035445

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0767%, amr)

Conditions

DCC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -15	GERP -3.3
Overall
CADD	0.137	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0767% Admixed American · 46/60,002 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0528%

Overall 0.0159% 257/1,612,808 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0767%	1,304
European (non-Finnish)	0.0161%	6,205
Remaining individualsnot grpmax-eligible	0.0112%	8,923
African / African-American	0.0107%	9,378
East Asian	0.00446%	22,436
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,596
South Asian	0.0022%	45,533
Finnishnot grpmax-eligible	0.00157%	63,834

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.Ser1223=
Coding: c.3669G>A
MANE Select: NM_005215
dbSNP: rs200234919
Type: single nucleotide variant
Location: chr18:53467943 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1223: 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

DCC-related disorder

Similar variants

DCC c.2828-1G>A Likely pathogenic ★ same condition
DCC c.3898+2T>C Likely pathogenic ★ same condition
DCC p.Arg501Ter Likely pathogenic ★ same condition
DCC p.Glu512Ter Likely pathogenic ★ same condition
DCC p.Trp508Ter Likely pathogenic ★ same condition
DCC p.Trp745Ter Likely pathogenic ★ same condition
DCC p.Pro1086Leu Uncertain significance ⚠ same condition
DCC p.Thr614Ile 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-ser1223 (accessed [today's date]).

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