Is RAD50 p.Arg644= (c.1932G>A) pathogenic?

RAD50 p.Arg644= (c.1932G>A) is classified Benign/Likely benign in RAD50 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-08-01). Rare (popmax 0.395%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Arg644= (c.1932G>A)?

RAD50 p.Arg644= (c.1932G>A) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome-like disorder, hereditary breast carcinoma (ClinVar).

How common is RAD50 p.Arg644= (c.1932G>A) in the general population?

RAD50 p.Arg644= (c.1932G>A) is rare (popmax 0.395%, mid) (gnomAD).

RAD50 p.Arg644=

c.1932G>A · rs375978877 · VCV185432

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.395%, mid)

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 -0.21	GERP -3.4, phastCons 0.012
Overall
CADD	5.208	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.395% Middle Eastern · 24/6,078 alleles

Filtering AF 0.272% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.232%

Overall 0.00583% 94/1,613,716 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.395%	253
Remaining individualsnot grpmax-eligible	0.0176%	5,680
South Asian	0.00878%	11,385
Admixed American	0.00667%	15,002
African / African-American	0.00534%	18,726
European (non-Finnish)	0.00364%	27,437

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.Arg644=
Coding: c.1932G>A
MANE Select: NM_005732
dbSNP: rs375978877
Type: single nucleotide variant
Location: chr5:132595007 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 6 PDB
Residue 644: the zinc-hook domain; 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

Also linked: Nijmegen breakage syndrome-like disorder hereditary breast carcinoma

Similar variants

RAD50 p.Arg644Gly Uncertain significance ★★ ⚠ same residue
RAD50 p.Arg644Lys Uncertain significance ★★ ⚠ same residue
RAD50 p.Arg644Ser 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-arg644 (accessed [today's date]).

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