SBF1 p.Pro1193=
c.3579C>T · rs374190021 · VCV738361
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.194%, afr)
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 -12 | GERP -5.2 |
| Overall | ||
| CADD | 0.483 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.194%
African / African-American · 145/74,924 alleles
Filtering AF
0.168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.0203%
326/1,609,580 alleles · rare
exomes 215/1,457,212 · genomes 111/152,368 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.194% | 517 |
| Middle Eastern | 0.139% | 721 |
| Admixed American | 0.0489% | 2,047 |
| Remaining individualsnot grpmax-eligible | 0.0385% | 2,598 |
| European (non-Finnish) | 0.00984% | 10,164 |
| East Asian | 0.00669% | 14,958 |
| South Asian | 0.0011% | 90,886 |
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.Pro1193=
- Coding
- c.3579C>T
- MANE Select
- NM_002972
- dbSNP
- rs374190021
- Type
- single nucleotide variant
- Location
- chr22:50459579 (GRCh38)
- Gene constraint
- LOEUF 0.381 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.72
- Residue 1193
- the myotubularin phosphatase domain
Similar variants
- 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
- SBF1 c.279+3C>T Uncertain significance ★★ same type
- SBF1 c.3904+6G>A 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-pro1193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown