RAD50 p.Gln537Ter
c.1609C>T · rs2149842334 · VCV2086651
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
hereditary neoplastic syndrome
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 10 of 25 |
| REVEL | 0.228 | benign-leaning |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.20 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 4, phastCons 1 |
| Overall | ||
| CADD | 37.0 | 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
- RAD50
- Protein
- p.Gln537Ter
- Coding
- c.1609C>T
- MANE Select
- NM_005732
- dbSNP
- rs2149842334
- Type
- single nucleotide variant
- Location
- chr5:132591380 (GRCh38)
- Gene constraint
- LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 82.83 · 6 PDB
Similar variants
- RAD50 p.Gln537= Likely benign ★★ same residue
- RAD50 p.Gln537Arg Uncertain significance ★ ⚠ same residue
- RAD50 p.Gln537His Uncertain significance ★ ⚠ same residue
- RAD50 c.1051+1G>A Likely pathogenic ★★ same condition
- RAD50 c.1052-1G>A Likely pathogenic ★★ same condition
- RAD50 c.1052-1G>T Pathogenic/Likely pathogenic ★★ same condition
- RAD50 c.1052-2A>C Likely pathogenic ★★ same condition
- RAD50 c.1245+1G>A Pathogenic/Likely pathogenic ★★ 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/rad50-p-gln537ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown