Is RAD50 p.Ser784= (c.2352T>C) pathogenic?

RAD50 p.Ser784= (c.2352T>C) is classified Benign/Likely benign in RAD50 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-08). Rare (popmax 0.31%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Ser784= (c.2352T>C)?

RAD50 p.Ser784= (c.2352T>C) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome-like disorder (ClinVar).

How common is RAD50 p.Ser784= (c.2352T>C) in the general population?

RAD50 p.Ser784= (c.2352T>C) is rare (popmax 0.31%, sas) (gnomAD).

RAD50 p.Ser784=

c.2352T>C · rs534731345 · VCV183904

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.31%, sas)

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 2.3	GERP 2.4, phastCons 1
Overall
CADD	10.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% South Asian · 282/91,084 alleles

Filtering AF 0.28% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.268%

Overall 0.0179% 289/1,613,944 alleles · rare exomes 270/1,461,636 · genomes 19/152,308 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.31%	323
Middle Eastern	0.0165%	6,058
Remaining individualsnot grpmax-eligible	0.008%	12,499
European (non-Finnish)	8.48e-05%	1,179,896

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.Ser784=
Coding: c.2352T>C
MANE Select: NM_005732
dbSNP: rs534731345
Type: single nucleotide variant
Location: chr5:132603444 (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

Also linked: Nijmegen breakage syndrome-like disorder

Similar variants

RAD50 p.Ser784Thr Uncertain significance ★★ ⚠ same residue
RAD50 p.Ser784Arg Uncertain significance ★ ⚠ same residue
RAD50 p.Ser784Asn Uncertain significance ★ ⚠ same residue
RAD50 p.Ser784Gly 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

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-ser784 (accessed [today's date]).

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