RHBDF2 p.Ala295=
c.885C>T · VCV3607317
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0353%, sas)
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 2.8 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 9.149 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0353%
South Asian · 32/90,578 alleles
Filtering AF
0.0257%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0224%
Overall
0.00242%
39/1,610,560 alleles · ultra-rare
exomes 39/1,458,230 · genomes 0/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0353% | 2,831 |
| Middle Eastern | 0.0166% | 6,028 |
| Remaining individualsnot grpmax-eligible | 0.00642% | 15,584 |
| European (non-Finnish) | 0.00017% | 589,484 |
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.Ala295=
- Coding
- c.885C>T
- MANE Select
- NM_001005498
- Type
- single nucleotide variant
- Location
- chr17:76477215 (GRCh38)
- Gene constraint
- LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.53 · 5 PDB
Similar variants
- RHBDF2 p.Ala295Thr 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-ala295 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown