HR p.Trp186Ter
c.557G>A · VCV4899699
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
HR-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 36.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- HR
- Protein
- p.Trp186Ter
- Coding
- c.557G>A
- MANE Select
- NM_005144
- Type
- single nucleotide variant
- Location
- chr8:22128614 (GRCh38)
- Gene constraint
- LOEUF 0.848 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 55.65
Similar variants
- HR p.Trp186Cys Uncertain significance ★ ⚠ same residue
- HR p.Arg819Ter Pathogenic/Likely pathogenic ★★ same condition
- HR p.Cys622Gly Pathogenic/Likely pathogenic ★★ same condition
- HRURF p.Met1Leu Pathogenic ★ same condition
- HR c.2122-10G>A Likely benign same condition
- HR p.Gly80= Likely benign same condition
- HR p.Leu488= Likely benign same condition
- HR p.Pro183= Likely benign same condition
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-trp186ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown