Is RAD50 p.Ser784Arg (c.2350A>C) pathogenic?

RAD50 p.Ser784Arg (c.2350A>C) is classified Uncertain significance in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: ambiguous (0.4497); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Ser784Arg (c.2350A>C)?

RAD50 p.Ser784Arg (c.2350A>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Ser784Arg (c.2350A>C) in the general population?

RAD50 p.Ser784Arg (c.2350A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD50 p.Ser784Arg (c.2350A>C)?

AlphaMissense predicts ambiguous (score 0.4497) — an in-silico prediction, not a clinical call.

RAD50 p.Ser784Arg

c.2350A>C · rs1750924370 · VCV1047413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4497 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4497	ambiguous
REVEL	0.092	moderately benign-leaning
SaProt	LLR -4.25	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 0.00013 · regional, not allelic
Overall
CADD	18.08	PHRED · no single calibrated threshold — expert panels disagree

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.Ser784Arg
Coding: c.2350A>C
MANE Select: NM_005732
dbSNP: rs1750924370
Type: single nucleotide variant
Location: chr5:132603442 (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.Ser784Thr Uncertain significance ★★ ⚠ same residue
RAD50 p.Ser784= Benign/Likely benign ★★ 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-ser784arg (accessed [today's date]).

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