SBDS p.Phe176=
c.528C>T · VCV4896138
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.41 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.34 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.9 | GERP 0.84, phastCons 1 |
| Overall | ||
| CADD | 16.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Overall
6.2e-05%
1/1,613,966 alleles · ultra-rare
exomes 0/1,461,708 · genomes 1/152,258 · joint denominator
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.Phe176=
- Coding
- c.528C>T
- MANE Select
- NM_016038
- Type
- single nucleotide variant
- Location
- chr7:66991233 (GRCh38)
- Gene constraint
- LOEUF 1.08 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.97 · 6 PDB
- Residue 176
- a β-strand
Similar variants
- SBDS c.258+1G>C Pathogenic ★★ same type
- SBDS c.258+2T>C Pathogenic/Likely pathogenic ★★ same type
- SBDS c.624+1G>A Likely pathogenic ★★ same type
- SBDS p.Arg218Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- SBDS p.Arg218Ter Pathogenic/Likely pathogenic ★★ same type
- SBDS p.Lys33Thr Pathogenic/Likely pathogenic ★★ same type
- SBDS p.Ser55Ter Likely pathogenic ★★ same type
- SBDS p.Tyr32Cys Likely pathogenic ★★ 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/sbds-p-phe176 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown