LINS1 p.Asp221=
c.663C>T · rs200665417 · VCV735563
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0312%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.21 | GERP -4.5 |
| Overall | ||
| CADD | 2.867 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
East Asian · 14/44,880 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.00149%
24/1,611,490 alleles · ultra-rare
exomes 18/1,459,202 · genomes 6/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0312% | 3,206 |
| Admixed American | 0.00167% | 59,970 |
| European (non-Finnish) | 0.000764% | 130,868 |
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
- LINS1
- Protein
- p.Asp221=
- Coding
- c.663C>T
- MANE Select
- NM_001040616
- dbSNP
- rs200665417
- Type
- single nucleotide variant
- Location
- chr15:100574210 (GRCh38)
- Gene constraint
- LOEUF 0.867 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
Similar variants
- LINS1 p.Asp221Asn Uncertain significance ★★ ⚠ same residue
- LINS1 p.Leu393Ter Pathogenic/Likely pathogenic ★★ same type
- LINS1 c.1394+4A>G Uncertain significance ★★ same type
- LINS1 p.Ala338Val Uncertain significance ★★ ⚠ same type
- LINS1 p.Asn433Ser Uncertain significance ★★ ⚠ same type
- LINS1 p.Asp630Asn Uncertain significance ★★ ⚠ same type
- LINS1 p.Ile494Thr Uncertain significance ★★ ⚠ same type
- LINS1 p.Leu757Ter 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/lins1-p-asp221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown