SPP2 p.Leu60=
c.180G>C · rs150743830 · VCV2076756
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0334%, 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 1.7 | GERP 0.8, phastCons 1 |
| Overall | ||
| CADD | 6.436 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0334%
African / African-American · 25/74,914 alleles
Filtering AF
0.0231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.00186%
30/1,613,830 alleles · ultra-rare
exomes 18/1,461,652 · genomes 12/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0334% | 2,997 |
| Middle Eastern | 0.0165% | 6,074 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Admixed American | 0.00167% | 59,972 |
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.Leu60=
- Coding
- c.180G>C
- MANE Select
- NM_006944
- dbSNP
- rs150743830
- Type
- single nucleotide variant
- Location
- chr2:234051065 (GRCh38)
- Gene constraint
- LOEUF 1.655 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.68
Similar variants
- SPP2 p.Leu60Val Benign ★ 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-leu60 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown