RPRD2 p.Ser761=
c.2283C>T · rs200404582 · VCV2639159
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.44%, nfe)
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 -0.86 | GERP -3.5, phastCons 0.003 |
| Overall | ||
| CADD | 4.572 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.44%
European (non-Finnish) · 5,188/1,179,856 alleles
Filtering AF
0.43%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.426%
Overall
0.359%
5,786/1,613,794 alleles · rare
exomes 5,438/1,461,702 · genomes 348/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.44% | 227 |
| Middle Eastern | 0.313% | 319 |
| Remaining individualsnot grpmax-eligible | 0.294% | 340 |
| Ashkenazi Jewishnot grpmax-eligible | 0.28% | 357 |
| Finnishnot grpmax-eligible | 0.214% | 467 |
| Admixed American | 0.17% | 588 |
| African / African-American | 0.06% | 1,665 |
| South Asian | 0.0308% | 3,252 |
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
- RPRD2
- Protein
- p.Ser761=
- Coding
- c.2283C>T
- MANE Select
- NM_015203
- dbSNP
- rs200404582
- Type
- single nucleotide variant
- Location
- chr1:150471231 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 48.32 · 3 PDB
- Residue 761
- the 'disordered' region
Similar variants
- RPRD2 p.Glu195= Benign ★★ same type
- RPRD2 p.Ala1083Ser Uncertain significance ★ ⚠ same type
- RPRD2 p.Ala1145Pro Uncertain significance ★ ⚠ same type
- RPRD2 p.Ala1149Val Uncertain significance ★ ⚠ same type
- RPRD2 p.Ala1165Val Uncertain significance ★ ⚠ same type
- RPRD2 p.Ala1251Thr Uncertain significance ★ ⚠ same type
- RPRD2 p.Ala140Val Uncertain significance ★ ⚠ same type
- RPRD2 p.Ala442Pro 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/rprd2-p-ser761 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown