RHBDF2 p.Ala397=
c.1191A>G · VCV3673735
Likely benign
Single submitter
Classification
Likely benign
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 carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -16 | GERP -3.6 |
| Overall | ||
| CADD | 1.108 | 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
Filtering AF
0.000503%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000368%
Overall
0.000877%
14/1,596,118 alleles · ultra-rare
exomes 11/1,443,980 · genomes 3/152,138 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| Finnishnot grpmax-eligible | 0.00319% | 31,353 |
| European (non-Finnish) | 0.000938% | 106,580 |
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.Ala397=
- Coding
- c.1191A>G
- MANE Select
- NM_001005498
- Type
- single nucleotide variant
- Location
- chr17:76475066 (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.Ala397Ser Uncertain significance ★★ ⚠ same residue
- RHBDF2 p.Ala397Thr 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.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-ala397 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown