RHBDF2 p.Ser488=
c.1464G>A · VCV4937117
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/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.83 | donor loss at this position · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.73 | loss · gain 0.02 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP 0.66, phastCons 1 |
| Overall | ||
| CADD | 19.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00446%
East Asian · 2/44,864 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00155%
25/1,612,048 alleles · very rare
exomes 24/1,459,898 · genomes 1/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00446% | 22,432 |
| European (non-Finnish) | 0.00187% | 53,607 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,380 |
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
- RHBDF2
- Protein
- p.Ser488=
- Coding
- c.1464G>A
- MANE Select
- NM_001005498
- Type
- single nucleotide variant
- Location
- chr17:76474373 (GRCh38)
- Gene constraint
- LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.53 · 5 PDB
- Residue 488
- an α-helix
Similar variants
- RHBDF2 p.Ile157Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- RHBDF2 c.151-27G>T Uncertain significance ★★ ⚠ same type
- RHBDF2 c.151-86G>A Uncertain significance ★★ ⚠ same type
- RHBDF2 p.Ala397Ser Uncertain significance ★★ ⚠ same type
- RHBDF2 p.Ala700Thr Uncertain significance ★★ ⚠ same type
- RHBDF2 p.Ala725Val Uncertain significance ★★ ⚠ same type
- RHBDF2 p.Arg113His Uncertain significance ★★ ⚠ same type
- RHBDF2 p.Arg205His 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/rhbdf2-p-ser488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown