Is RAD50 p.Val697Ile (c.2089G>A) pathogenic?

RAD50 p.Val697Ile (c.2089G>A) is classified Uncertain significance in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-22). AlphaMissense: likely benign (0.1839); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Val697Ile (c.2089G>A)?

RAD50 p.Val697Ile (c.2089G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Val697Ile (c.2089G>A) in the general population?

RAD50 p.Val697Ile (c.2089G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD50 p.Val697Ile (c.2089G>A)?

AlphaMissense predicts likely benign (score 0.1839) — an in-silico prediction, not a clinical call.

RAD50 p.Val697Ile

c.2089G>A · VCV3429490

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1839 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1839	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 3.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 0.00013 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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.Val697Ile
Coding: c.2089G>A
MANE Select: NM_005732
Type: single nucleotide variant
Location: chr5:132595692 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 6 PDB
Residue 697: the zinc-hook domain; a UniProt-annotated variant site (in); an α-helix

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.Val697= Benign/Likely benign ★★ 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
RAD50 c.129+1G>A Likely pathogenic ★★ same condition
RAD50 c.129+1G>T 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-val697ile (accessed [today's date]).

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