SPP2 p.Pro100=
c.300C>T · rs76941072 · VCV1170674
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.78%, 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 -15 | GERP -11 |
| Overall | ||
| CADD | 0.261 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.78%
European (non-Finnish) · 20,987/1,179,814 alleles
Filtering AF
1.76%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.75%
Overall
1.46%
23,501/1,613,846 alleles · low-frequency
exomes 21,726/1,461,600 · genomes 1,775/152,246 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 1.78% | 56 |
| Remaining individualsnot grpmax-eligible | 1.45% | 69 |
| Admixed American | 1.24% | 81 |
| Middle Eastern | 0.891% | 112 |
| Finnishnot grpmax-eligible | 0.69% | 145 |
| Ashkenazi Jewishnot grpmax-eligible | 0.402% | 249 |
| African / African-American | 0.297% | 336 |
| South Asian | 0.0319% | 3,139 |
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.Pro100=
- Coding
- c.300C>T
- MANE Select
- NM_006944
- dbSNP
- rs76941072
- Type
- single nucleotide variant
- Location
- chr2:234058925 (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-pro100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown