Is RAD50 p.Pro387fs (c.1158_1159del) pathogenic?

RAD50 p.Pro387fs (c.11581159del) is classified Pathogenic in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-12). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Pro387fs (c.1158_1159del)?

RAD50 p.Pro387fs (c.1158_1159del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Pro387fs (c.1158_1159del) in the general population?

RAD50 p.Pro387fs (c.1158_1159del) is very rare (popmax 0.00223%, eas) (gnomAD).

RAD50 p.Pro387fs

c.1158_1159del · rs1199799880 · VCV1735704

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 25
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.5	GERP 3.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Overall 6.84e-05% 1/1,461,744 alleles · very rare

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: RAD50
Protein: p.Pro387fs
Coding: c.1158_1159del
MANE Select: NM_005732
dbSNP: rs1199799880
Type: Deletion
Location: chr5:132588793 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 6 PDB

Full RAD50 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAD50 p.Pro387Leu Uncertain significance ★★ ⚠ same residue
RAD50 p.Pro387Ser Uncertain significance ★★ ⚠ same residue
RAD50 p.Pro387Ala Uncertain significance ★ ⚠ same residue
RAD50 p.Pro387= Likely benign ★ same residue
RAD50 c.129+1del Pathogenic ★★ same condition
RAD50 c.3160_3164+8del Likely pathogenic ★★ same condition
RAD50 p.Arg903fs Pathogenic ★★ same condition
RAD50 p.Asn1070fs 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-pro387fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown