LSS p.Phe596=
c.1788C>T · rs114786885 · VCV769142
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.631%, 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 -4.5 | GERP -3.5 |
| Overall | ||
| CADD | 8.388 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.631%
African / African-American · 473/74,970 alleles
Filtering AF
0.584%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.565%
Overall
0.0323%
521/1,613,608 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.631% | 158 |
| Remaining individualsnot grpmax-eligible | 0.0416% | 2,404 |
| Middle Eastern | 0.033% | 3,030 |
| Admixed American | 0.0233% | 4,286 |
| South Asian | 0.0011% | 91,048 |
| European (non-Finnish) | 0.000424% | 235,992 |
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.Phe596=
- Coding
- c.1788C>T
- MANE Select
- NM_002340
- dbSNP
- rs114786885
- Type
- single nucleotide variant
- Location
- chr21:46195705 (GRCh38)
- Gene constraint
- LOEUF 1.05 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 98.05 · 2 PDB
- Residue 596
- a UniProt-annotated variant site (in apmr4; loss of protein expression); an α-helix
Similar variants
- 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
- LSS p.Arg260His 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-phe596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown