SPP2 p.Trp136Arg
c.406T>A · VCV4745506
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6716 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6716 | likely pathogenic |
|---|---|---|
| REVEL | 0.228 | benign-leaning |
| SaProt | LLR -3.01 | tolerated |
| ⇒ AlphaMissense calls this damaging; REVEL and SaProt do not. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 5, phastCons 1 |
| Regional constraint | o/e 1.02 | unconstrained · MANE · 19 kb · p 0.75 · regional, not allelic |
| Overall | ||
| CADD | 19.91 | 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
- SPP2
- Protein
- p.Trp136Arg
- Coding
- c.406T>A
- MANE Select
- NM_006944
- Type
- single nucleotide variant
- Location
- chr2:234060441 (GRCh38)
- Gene constraint
- LOEUF 1.655 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.68
Similar variants
- SPP2 p.Trp136Cys Uncertain significance ★★ ⚠ same residue
- SPP2 c.210+1G>A Uncertain significance ★★ same type
- SPP2 c.500-1G>T Uncertain significance ★★ same type
- SPP2 c.86-1G>T Uncertain significance ★★ same type
- SPP2 p.Ala101Thr Uncertain significance ★★ ⚠ same type
- SPP2 p.Arg133Cys Uncertain significance ★★ ⚠ same type
- SPP2 p.Arg161Ile Uncertain significance ★★ ⚠ same type
- SPP2 p.Arg201Pro 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/spp2-p-trp136arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown