HR p.Pro822=
c.2466G>A · VCV4725865
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0328%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.59 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.27 | gain · loss 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -2.6 |
| Overall | ||
| CADD | 2.372 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0328%
African / African-American · 24/73,138 alleles
Filtering AF
0.0226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0192%
Overall
0.00309%
48/1,551,816 alleles · ultra-rare
exomes 32/1,399,616 · genomes 16/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0328% | 3,047 |
| Remaining individualsnot grpmax-eligible | 0.00832% | 12,022 |
| Admixed American | 0.00391% | 25,557 |
| East Asian | 0.00243% | 41,084 |
| European (non-Finnish) | 0.00131% | 76,516 |
| South Asian | 0.00119% | 84,290 |
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.Pro822=
- Coding
- c.2466G>A
- MANE Select
- NM_005144
- Type
- single nucleotide variant
- Location
- chr8:22120860 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
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-pro822 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown