SECISBP2 p.Pro425=
c.1275G>A · rs769313577 · VCV706803
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0433%, amr)
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 1.3 | GERP -3.4, phastCons 0.96 |
| Overall | ||
| CADD | 11.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0433%
Admixed American · 26/59,996 alleles
Filtering AF
0.0303%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.026%
Overall
0.00459%
74/1,613,336 alleles · ultra-rare
exomes 71/1,461,196 · genomes 3/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0433% | 2,308 |
| South Asian | 0.0395% | 2,530 |
| East Asian | 0.0178% | 5,608 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,458 |
| European (non-Finnish) | 0.000254% | 393,188 |
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
- SECISBP2
- Protein
- p.Pro425=
- Coding
- c.1275G>A
- MANE Select
- NM_024077
- dbSNP
- rs769313577
- Type
- single nucleotide variant
- Location
- chr9:89339926 (GRCh38)
- Gene constraint
- LOEUF 1.198 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.54 · 2 PDB
- Residue 425
- the 'disordered' region
Similar variants
- SECISBP2 p.Pro425Arg Uncertain significance ★ ⚠ same residue
- SECISBP2 p.Pro425Leu Uncertain significance ★ ⚠ same residue
- SECISBP2 p.Gln799Lys Uncertain significance ★★ ⚠ same type
- SECISBP2 p.Ser346Phe Uncertain significance ★★ ⚠ same type
- SECISBP2 p.Ala141Val Benign ★★ same type
- SECISBP2 p.Ala772= Benign ★★ same type
- SECISBP2 p.Gly492Val Benign ★★ same type
- SEMA4D c.1883-64C>T Likely benign ★★ 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/secisbp2-p-pro425 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown