RHBDF2 p.Pro503=
c.1509C>T · rs758642827 · VCV734961
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.086%, amr)
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 2.3 | GERP -3.3, phastCons 1 |
| Overall | ||
| CADD | 6.475 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.086%
Admixed American · 51/59,322 alleles
Filtering AF
0.0671%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0605%
Overall
0.00324%
52/1,607,146 alleles · ultra-rare
exomes 47/1,454,936 · genomes 5/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.086% | 1,163 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,250 |
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.Pro503=
- Coding
- c.1509C>T
- MANE Select
- NM_001005498
- dbSNP
- rs758642827
- Type
- single nucleotide variant
- Location
- chr17:76474098 (GRCh38)
- Gene constraint
- LOEUF 0.545 · pLI 0.15 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.53 · 5 PDB
- Residue 503
- a β-strand
Similar variants
- RHBDF2 p.Pro503Leu Uncertain significance ★ ⚠ same residue
- RHBDF2 p.Pro503Ser 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
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-pro503 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown