HR p.Ala645=
c.1935G>A · VCV3645806
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.026%, afr)
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 -12 | GERP -3.1 |
| Overall | ||
| CADD | 0.322 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.026%
African / African-American · 19/73,174 alleles
Filtering AF
0.017%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0141%
Overall
0.00232%
36/1,554,014 alleles · ultra-rare
exomes 27/1,401,806 · genomes 9/152,208 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.026% | 3,851 |
| Remaining individualsnot grpmax-eligible | 0.00332% | 30,106 |
| European (non-Finnish) | 0.00131% | 76,585 |
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.Ala645=
- Coding
- c.1935G>A
- MANE Select
- NM_005144
- Type
- single nucleotide variant
- Location
- chr8:22122860 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
Similar variants
- HR p.Ala645Glu Uncertain significance ★ ⚠ same residue
- HR p.Ala645Ser Uncertain significance ★ ⚠ same residue
- HR p.Ala645Val Uncertain significance ★ ⚠ same residue
- HR p.Ala645Thr Likely benign ★ same residue
- 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
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-ala645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown