SBF1 p.Pro957=
c.2871G>A · rs757816344 · VCV1176452
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00669%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.40 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.24 | gain · loss 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -6.9 | GERP -4.6 |
| Overall | ||
| CADD | 15.51 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
African / African-American · 5/74,794 alleles
Filtering AF
0.00255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00162%
Overall
0.00161%
26/1,611,914 alleles · very rare
exomes 23/1,460,000 · genomes 3/151,914 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00669% | 14,959 |
| South Asian | 0.0033% | 30,333 |
| European (non-Finnish) | 0.00153% | 65,491 |
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
- SBF1
- Protein
- p.Pro957=
- Coding
- c.2871G>A
- MANE Select
- NM_002972
- dbSNP
- rs757816344
- Type
- single nucleotide variant
- Location
- chr22:50461255 (GRCh38)
- Gene constraint
- LOEUF 0.381 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.72
- Residue 957
- the gram domain
Similar variants
- SBF1 p.Pro957Ala Uncertain significance ★ ⚠ same residue
- SBF1 p.Pro957Leu Uncertain significance ★ ⚠ same residue
- SBF1 c.3826+1G>A Pathogenic/Likely pathogenic ★★ same type
- SBF1 p.Met417Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- SBF1 c.1431+6A>T Uncertain significance ★★ same type
- SBF1 c.1636+4C>T Uncertain significance ★★ same type
- SBF1 c.1899+3G>A Uncertain significance ★★ same type
- SBF1 c.2643+6C>T 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/sbf1-p-pro957 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown