DCC p.Ala218=
c.654C>A · rs142720578 · VCV745786
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0999%, sas)
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 3.2 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 12.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0999%
South Asian · 91/91,082 alleles
Filtering AF
0.0833%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0771%
Overall
0.0251%
405/1,614,050 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0999% | 1,001 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0405% | 2,467 |
| Middle Eastern | 0.033% | 3,030 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,907 |
| European (non-Finnish) | 0.0225% | 4,436 |
| Finnishnot grpmax-eligible | 0.0172% | 5,812 |
| Admixed American | 0.00667% | 15,001 |
| East Asian | 0.00446% | 22,435 |
| African / African-American | 0.00133% | 75,040 |
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.Ala218=
- Coding
- c.654C>A
- MANE Select
- NM_005215
- dbSNP
- rs142720578
- Type
- single nucleotide variant
- Location
- chr18:52906285 (GRCh38)
- Gene constraint
- LOEUF 0.414 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 68.60 · 9 PDB
- Residue 218
- the ig-like c2-type 2 domain
Similar variants
- 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
- DCC p.Gly1294Arg Uncertain significance ★★ ⚠ same type
- DCC p.Gly55Arg 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-ala218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown