SPPL2A p.Pro91=
c.273A>G · rs1204721298 · VCV2912444
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0033%, sas)
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 -1.7 | GERP -2.6 |
| Overall | ||
| CADD | 6.338 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0033%
South Asian · 3/90,896 alleles
Filtering AF
0.000877%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000372%
6/1,612,362 alleles · very rare
exomes 6/1,460,020 · genomes 0/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0033% | 30,299 |
| European (non-Finnish) | 0.000254% | 393,099 |
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
- SPPL2A
- Protein
- p.Pro91=
- Coding
- c.273A>G
- MANE Select
- NM_032802
- dbSNP
- rs1204721298
- Type
- single nucleotide variant
- Location
- chr15:50748775 (GRCh38)
- Gene constraint
- LOEUF 1.074 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 79.28 · 2 PDB
- Residue 91
- the pa domain
Similar variants
- SPPL2A p.Ala179Val Uncertain significance ★★ ⚠ same type
- SPPL2A p.Ala298Val Uncertain significance ★★ ⚠ same type
- SPPL2A p.Ala480Thr Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg281Cys Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg281His Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg424Thr Uncertain significance ★★ ⚠ same type
- SPPL2A p.Arg483His Uncertain significance ★★ same type
- SPPL2A p.Asn66Thr 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/sppl2a-p-pro91 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown