RPRD2 p.Pro1448=
c.4344G>A · rs375980931 · VCV3156179
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, 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 3.8 | GERP 0.52, phastCons 1 |
| Overall | ||
| CADD | 11.98 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Middle Eastern · 1/5,972 alleles
Filtering AF
0.00402%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00362%
Overall
0.00471%
76/1,613,110 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0167% | 5,972 |
| East Asian | 0.00891% | 11,221 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,485 |
| European (non-Finnish) | 0.00509% | 19,660 |
| Admixed American | 0.00334% | 29,953 |
| African / African-American | 0.00267% | 37,431 |
| South Asian | 0.0022% | 45,526 |
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.Pro1448=
- Coding
- c.4344G>A
- MANE Select
- NM_015203
- dbSNP
- rs375980931
- Type
- single nucleotide variant
- Location
- chr1:150473292 (GRCh38)
- Gene constraint
- LOEUF 0.145 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 48.32 · 3 PDB
- Residue 1448
- 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-pro1448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown