RBP4 p.Ala166=
c.498G>A · rs369378480 · VCV1089244
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00446%, eas)
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 -7.7 | GERP -4.2 |
| Overall | ||
| CADD | 0.776 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,888 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00174%
28/1,613,622 alleles · very rare
exomes 22/1,461,430 · genomes 6/152,192 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,444 |
| European (non-Finnish) | 0.00195% | 51,306 |
| Admixed American | 0.00167% | 60,010 |
| African / African-American | 0.00133% | 74,916 |
| South Asian | 0.0011% | 91,052 |
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
- RBP4
- Protein
- p.Ala166=
- Coding
- c.498G>A
- MANE Select
- NM_006744
- dbSNP
- rs369378480
- Type
- single nucleotide variant
- Location
- chr10:93593893 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.87 (gnomAD)
- Structure
- AlphaFold pLDDT 90.33 · 24 PDB
- Residue 166
- an α-helix
Similar variants
- RBP4 p.Ala166Val Uncertain significance ★ ⚠ same residue
- RBP4 p.Ala6Val Uncertain significance ★★ ⚠ same type
- RBP4 p.Arg173Trp Uncertain significance ★★ ⚠ same type
- RBP4 p.Arg20Cys Uncertain significance ★★ ⚠ same type
- RBP4 p.Arg37Gly Uncertain significance ★★ ⚠ same type
- RBP4 p.Asn189Ser Uncertain significance ★★ ⚠ same type
- RBP4 p.Asp130Asn Uncertain significance ★★ ⚠ same type
- RBP4 p.Asp158Tyr 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/rbp4-p-ala166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown