LINS1 p.Cys493=
c.1479T>C · rs144513217 · VCV435759
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
rare (popmax 0.344%, mid)
Conditions
1
Inborn genetic diseases
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 0.99 | GERP -3.7, phastCons 0.51 |
| Overall | ||
| CADD | 5.416 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.344%
Middle Eastern · 20/5,812 alleles
Filtering AF
0.228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.191%
Overall
0.0328%
510/1,557,222 alleles · rare
exomes 451/1,404,860 · genomes 59/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.344% | 291 |
| Remaining individualsnot grpmax-eligible | 0.0828% | 1,208 |
| Admixed American | 0.0688% | 1,454 |
| European (non-Finnish) | 0.0328% | 3,049 |
| South Asian | 0.0216% | 4,635 |
| African / African-American | 0.00684% | 14,615 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00365% | 27,362 |
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.Cys493=
- Coding
- c.1479T>C
- MANE Select
- NM_001040616
- dbSNP
- rs144513217
- Type
- single nucleotide variant
- Location
- chr15:100570033 (GRCh38)
- Gene constraint
- LOEUF 0.867 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.44
Similar variants
- LINS1 c.1394+4A>G Uncertain significance ★★ same condition
- LINS1 p.Ala338Val Uncertain significance ★★ ⚠ same condition
- LINS1 p.Asn433Ser Uncertain significance ★★ ⚠ same condition
- LINS1 p.Asp630Asn Uncertain significance ★★ ⚠ same condition
- LINS1 p.Ile494Thr Uncertain significance ★★ ⚠ same condition
- LINS1 p.Leu757Ter Uncertain significance ★★ same condition
- LINS1 p.Met449Ile Uncertain significance ★★ ⚠ same condition
- LINS1 p.Ala331Val Benign ★★ 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/lins1-p-cys493 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown