SPRED1 p.Pro415=
c.1245A>G · rs934682906 · VCV2196085
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Conditions
2
Cardiovascular phenotype
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 -2.6 | GERP -2 |
| Overall | ||
| CADD | 6.418 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,916 alleles
Filtering AF
0.000615%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.000867%
14/1,613,996 alleles · very rare
exomes 13/1,461,840 · genomes 1/152,156 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,916 |
| European (non-Finnish) | 0.0011% | 90,770 |
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
- SPRED1
- Protein
- p.Pro415=
- Coding
- c.1245A>G
- MANE Select
- NM_152594
- dbSNP
- rs934682906
- Type
- single nucleotide variant
- Location
- chr15:38351574 (GRCh38)
- Gene constraint
- LOEUF 0.496 · pLI 0.98 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 63.67 · 3 PDB
- Residue 415
- the spr domain; the 'required for interaction with tesk1' region
Similar variants
- SPRED1 p.Arg117Ter Pathogenic ★★ same condition
- SPRED1 p.Arg16Ter Pathogenic ★★ same condition
- SPRED1 p.Arg18Ter Pathogenic ★★ same condition
- SPRED1 p.Arg24Ter Pathogenic ★★ same condition
- SPRED1 p.Arg251Ter Pathogenic/Likely pathogenic ★★ same condition
- SPRED1 p.Arg325Ter Pathogenic/Likely pathogenic ★★ same condition
- SPRED1 p.Arg403Ter Pathogenic/Likely pathogenic ★★ same condition
- SPRED1 p.Arg64Ter Pathogenic ★★ same condition
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/spred1-p-pro415 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown