HR p.Ser133=
c.399T>C · VCV4899700
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00169%, amr)
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 2.5 | GERP -0.71, phastCons 1 |
| Overall | ||
| CADD | 9.543 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00169%
Admixed American · 1/59,108 alleles
Filtering AF
0.000616%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000474%
Overall
0.00087%
14/1,609,052 alleles · very rare
exomes 12/1,456,884 · genomes 2/152,168 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00169% | 59,108 |
| European (non-Finnish) | 0.0011% | 90,635 |
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.Ser133=
- Coding
- c.399T>C
- MANE Select
- NM_005144
- Type
- single nucleotide variant
- Location
- chr8:22128772 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
Similar variants
- HR p.Ser133Asn Uncertain significance ★ ⚠ 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
- HR c.*180G>A Uncertain significance ★★ same type
- HR c.*295G>A Uncertain significance ★★ same type
- HR p.Ala1188Asp 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-ser133 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown