SPP2 p.Ile206=
c.618A>C · VCV4960687
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00212%, nfe)
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 -0.7 | GERP -3.2 |
| Overall | ||
| CADD | 0.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00212%
European (non-Finnish) · 25/1,179,572 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00155%
25/1,613,530 alleles · very rare
exomes 25/1,461,172 · genomes 0/152,358 · joint denominator
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
- SPP2
- Protein
- p.Ile206=
- Coding
- c.618A>C
- MANE Select
- NM_006944
- Type
- single nucleotide variant
- Location
- chr2:234069995 (GRCh38)
- Gene constraint
- LOEUF 1.655 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.68
Similar variants
- 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
- SPP2 p.Arg62Gln 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-ile206 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown