HR p.Ala243=
c.729C>T · rs79783229 · VCV2049467
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.325%, 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 -2.1 | GERP -3.8 |
| Overall | ||
| CADD | 1.294 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.325%
African / African-American · 244/75,040 alleles
Filtering AF
0.292%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.279%
Overall
0.0263%
422/1,607,320 alleles · rare
exomes 282/1,455,018 · genomes 140/152,302 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.325% | 308 |
| Remaining individualsnot grpmax-eligible | 0.056% | 1,785 |
| Admixed American | 0.015% | 6,669 |
| European (non-Finnish) | 0.0107% | 9,365 |
| South Asian | 0.00659% | 15,181 |
| Finnishnot grpmax-eligible | 0.00349% | 28,635 |
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.Ala243=
- Coding
- c.729C>T
- MANE Select
- NM_005144
- dbSNP
- rs79783229
- Type
- single nucleotide variant
- Location
- chr8:22127713 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
- Residue 243
- 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-ala243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown