Is RAD50 p.Val348= (c.1044T>G) pathogenic?

RAD50 p.Val348= (c.1044T>G) is classified Likely benign in RAD50 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-23). Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Val348= (c.1044T>G)?

RAD50 p.Val348= (c.1044T>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Val348= (c.1044T>G) in the general population?

RAD50 p.Val348= (c.1044T>G) is very rare (popmax 0.00167%, amr) (gnomAD).

RAD50 p.Val348=

c.1044T>G · rs1750629183 · VCV1665189

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 2.4	GERP 2.4, phastCons 1
Overall
CADD	7.708	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,998 alleles

Overall 0.000657% 1/152,188 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.Val348=
Coding: c.1044T>G
MANE Select: NM_005732
dbSNP: rs1750629183
Type: single nucleotide variant
Location: chr5:132588082 (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.Val348Ile Uncertain significance ★★ ⚠ same residue
RAD50 p.Val348Leu Uncertain significance ★ ⚠ same residue
RAD50 p.Val348Phe 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-val348 (accessed [today's date]).

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