LSS p.Pro282=
c.846C>T · rs114975335 · VCV770674
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.06%, afr)
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 -12 | GERP -3.3 |
| Overall | ||
| CADD | 0.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.06%
African / African-American · 2,290/74,932 alleles
Filtering AF
2.95%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.91%
Overall
0.179%
2,883/1,612,450 alleles · low-frequency
exomes 1,483/1,460,274 · genomes 1,400/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.06% | 33 |
| Remaining individualsnot grpmax-eligible | 0.263% | 381 |
| Admixed American | 0.197% | 508 |
| Ashkenazi Jewishnot grpmax-eligible | 0.142% | 703 |
| Middle Eastern | 0.0991% | 1,009 |
| European (non-Finnish) | 0.021% | 4,755 |
| East Asian | 0.00892% | 11,210 |
| Finnishnot grpmax-eligible | 0.00785% | 12,738 |
| South Asian | 0.0066% | 15,157 |
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
- LSS
- Protein
- p.Pro282=
- Coding
- c.846C>T
- MANE Select
- NM_002340
- dbSNP
- rs114975335
- Type
- single nucleotide variant
- Location
- chr21:46215731 (GRCh38)
- Gene constraint
- LOEUF 1.05 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 98.05 · 2 PDB
- Residue 282
- a UniProt-annotated variant site (in apmr4; loss of protein expression); an α-helix
Similar variants
- LSS p.Pro282Ser Uncertain significance ★ ⚠ same residue
- LSS p.Arg177Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- LSS p.Asn516Ser Likely pathogenic ★★ ⚠ same type
- LSS p.Trp216Ter Pathogenic ★★ same type
- LSS p.Tyr286Cys Likely pathogenic ★★ ⚠ same type
- LSS p.Ala399Val Uncertain significance ★★ ⚠ same type
- LSS p.Ala73Thr Uncertain significance ★★ ⚠ same type
- LSS p.Arg129Gln 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/lss-p-pro282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown