LSS p.Pro366Arg
c.1097C>G · VCV3728010
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1185 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1185 | likely benign |
|---|---|---|
| REVEL | 0.205 | benign-leaning |
| SaProt | LLR -10.59 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense and REVEL do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.4 | GERP -0.39, phastCons 1 |
| Regional constraint | o/e 0.94 | unconstrained · MANE · 38 kb · p 0.045 · regional, not allelic |
| Overall | ||
| CADD | 20.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- LSS
- Protein
- p.Pro366Arg
- Coding
- c.1097C>G
- MANE Select
- NM_002340
- Type
- single nucleotide variant
- Location
- chr21:46213750 (GRCh38)
- Gene constraint
- LOEUF 1.05 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 98.05 · 2 PDB
- Residue 366
- 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-pro366arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown