HR p.Pro417=
c.1251C>T · VCV4752157
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0911%, 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 -5.3 | GERP -3.5 |
| Overall | ||
| CADD | 0.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0911%
South Asian · 83/91,080 alleles
Filtering AF
0.0752%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0694%
Overall
0.0118%
191/1,612,826 alleles · ultra-rare
exomes 176/1,460,568 · genomes 15/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0911% | 1,097 |
| Middle Eastern | 0.0329% | 3,041 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,809 |
| European (non-Finnish) | 0.00737% | 13,563 |
| African / African-American | 0.00667% | 14,990 |
| Admixed American | 0.005% | 20,005 |
| East Asian | 0.00445% | 22,447 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,594 |
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
- HR
- Protein
- p.Pro417=
- Coding
- c.1251C>T
- MANE Select
- NM_005144
- Type
- single nucleotide variant
- Location
- chr8:22127191 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
- Residue 417
- the 'disordered' region
Similar variants
- HR c.-320T>A Pathogenic/Likely pathogenic ★★ same type
- HR p.Arg819Ter Pathogenic/Likely pathogenic ★★ same type
- HR p.Arg940Ter Pathogenic ★★ same type
- HR p.Cys622Gly Pathogenic/Likely pathogenic ★★ same type
- HR c.*180G>A Uncertain significance ★★ same type
- HR c.*295G>A Uncertain significance ★★ same type
- HR p.Ala1188Asp Uncertain significance ★★ ⚠ same type
- HR p.Ala511Thr 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/hr-p-pro417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown