DSCAM p.Ile721=
c.2163C>T · rs372883195 · VCV780195
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0867%, amr)
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 -2.4 | GERP -3.5 |
| Overall | ||
| CADD | 8.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0867%
Admixed American · 52/59,972 alleles
Filtering AF
0.0679%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0611%
Overall
0.0117%
189/1,613,796 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0867% | 1,153 |
| Middle Eastern | 0.0495% | 2,021 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,944 |
| European (non-Finnish) | 0.00966% | 10,349 |
| African / African-American | 0.008% | 12,505 |
| East Asian | 0.00446% | 22,427 |
| South Asian | 0.0033% | 30,340 |
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
- DSCAM
- Protein
- p.Ile721=
- Coding
- c.2163C>T
- MANE Select
- NM_001389
- dbSNP
- rs372883195
- Type
- single nucleotide variant
- Location
- chr21:40296074 (GRCh38)
- Gene constraint
- LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.98 · 1 PDB
- Residue 721
- the ig-like c2-type 8 domain; a disulfide bond; a β-strand
Similar variants
- DSCAM p.Ser682Arg Uncertain significance ★★ ⚠ same type
- DSCAM c.5383+9T>A Benign ★★ same type
- DSCAM p.Ala153= Benign ★★ same type
- DSCAM p.Arg1798= Benign/Likely benign ★★ same type
- DSCAM p.Asn1250= Benign ★★ same type
- DSCAM p.Asn576= Benign/Likely benign ★★ same type
- DSCAM p.Asp185= Benign/Likely benign ★★ same type
- DSCAM p.Gln582= Benign ★★ 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/dscam-p-ile721 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown