SBDS p.Leu239=
c.717G>A · VCV3437519
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, afr)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.3 | GERP 0.9, phastCons 1 |
| Overall | ||
| CADD | 10.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
African / African-American · 10/75,038 alleles
Filtering AF
0.00722%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00549%
Overall
0.00254%
41/1,613,792 alleles · ultra-rare
exomes 39/1,461,512 · genomes 2/152,280 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0133% | 7,504 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,418 |
| European (non-Finnish) | 0.00203% | 49,166 |
| South Asian | 0.0011% | 91,080 |
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
- SBDS
- Protein
- p.Leu239=
- Coding
- c.717G>A
- MANE Select
- NM_016038
- Type
- single nucleotide variant
- Location
- chr7:66988407 (GRCh38)
- Gene constraint
- LOEUF 1.08 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 6 PDB
- Residue 239
- a β-strand
Similar variants
- SBDS p.Lys33Thr Pathogenic/Likely pathogenic ★★ same condition
- SBDS p.Arg22Cys Uncertain significance ★★ ⚠ same condition
- SBDS p.Asp246Asn Uncertain significance ★★ ⚠ same condition
- SBDS p.Cys216Tyr Uncertain significance ★★ ⚠ same condition
- SBDS p.Ile111Val Uncertain significance ★★ ⚠ same condition
- SBDS p.Ile224Thr Uncertain significance ★★ ⚠ same condition
- SBDS p.Lys240Arg Uncertain significance ★★ ⚠ same condition
- SBDS p.Thr129Ser Uncertain significance ★★ 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/sbds-p-leu239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown