Is RAD50 p.Leu1237fs (c.3710_3714del) pathogenic?

RAD50 p.Leu1237fs (c.37103714del) is classified Pathogenic in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-17). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Leu1237fs (c.3710_3714del)?

RAD50 p.Leu1237fs (c.3710_3714del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Leu1237fs (c.3710_3714del) in the general population?

RAD50 p.Leu1237fs (c.3710_3714del) is no gnomAD frequency available for this variant (gnomAD).

RAD50 p.Leu1237fs

c.3710_3714del · rs2479435286 · VCV1734195

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (24 of 25, 43 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.01	GERP -3.1, phastCons 0.95

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RAD50
Protein: p.Leu1237fs
Coding: c.3710_3714del
MANE Select: NM_005732
dbSNP: rs2479435286
Type: Deletion
Location: chr5:132640762 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 6 PDB
Residue 1237: a UniProt-annotated variant site (in nbsld)

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.Leu1237Phe Uncertain significance ★ ⚠ 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
RAD50 p.Asn1118fs Pathogenic/Likely pathogenic ★★ same condition
RAD50 p.Asn412fs Pathogenic ★★ same condition
RAD50 p.Asn931fs 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-leu1237fs (accessed [today's date]).

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