RHBDF2 p.Leu749=
c.2247C>T · rs148859527 · VCV1617785
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0126%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.4 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 11.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0126%
South Asian · 11/87,606 alleles
Filtering AF
0.00702%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00541%
Overall
0.00353%
56/1,587,104 alleles · ultra-rare
exomes 50/1,434,854 · genomes 6/152,250 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0126% | 7,964 |
| Remaining individualsnot grpmax-eligible | 0.00488% | 20,513 |
| European (non-Finnish) | 0.00334% | 29,915 |
| African / African-American | 0.00268% | 37,269 |
| Admixed American | 0.00183% | 54,752 |
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.Leu749=
- Coding
- c.2247C>T
- MANE Select
- NM_001005498
- dbSNP
- rs148859527
- Type
- single nucleotide variant
- Location
- chr17:76471870 (GRCh38)
- Gene constraint
- LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.53 · 5 PDB
- Residue 749
- an α-helix
Similar variants
- RHBDF2 p.Leu749Val Uncertain significance ★ ⚠ same residue
- 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
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-leu749 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown