Is RAD50 p.His397= (c.1191C>T) pathogenic?

RAD50 p.His397= (c.1191C>T) is classified Likely benign in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-27). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.His397= (c.1191C>T)?

RAD50 p.His397= (c.1191C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.His397= (c.1191C>T) in the general population?

RAD50 p.His397= (c.1191C>T) is absent from gnomAD v4.1 (gnomAD).

RAD50 p.His397=

c.1191C>T · rs2149841152 · VCV1157249

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP 2, phastCons 0.99
Overall
CADD	7.127	PHRED · no single calibrated threshold — expert panels disagree

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.His397=
Coding: c.1191C>T
MANE Select: NM_005732
dbSNP: rs2149841152
Type: single nucleotide variant
Location: chr5:132588826 (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.His397Arg Uncertain significance ★★ ⚠ same residue
RAD50 p.His397Gln Uncertain significance ★ ⚠ same residue
RAD50 p.His397Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD50 p.His397Tyr Uncertain significance ★ ⚠ same residue
RAD50 p.His397fs Pathogenic ★ 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

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-his397 (accessed [today's date]).

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