Is RAD50 p.Arg13Pro (c.38G>C) pathogenic?

RAD50 p.Arg13Pro (c.38G>C) is classified Uncertain significance in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-08). AlphaMissense: likely pathogenic (0.9989); Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Arg13Pro (c.38G>C)?

RAD50 p.Arg13Pro (c.38G>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Arg13Pro (c.38G>C) in the general population?

RAD50 p.Arg13Pro (c.38G>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about RAD50 p.Arg13Pro (c.38G>C)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

RAD50 p.Arg13Pro

c.38G>C · VCV4862825

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic · top 1% in RAD50
REVEL	0.808	moderately pathogenic-leaning
SaProt	LLR -16.06	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 3.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 38 kb · p 0.02 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00133% African / African-American · 1/74,936 alleles

Overall 6.2e-05% 1/1,614,006 alleles · very rare exomes 0/1,461,774 · genomes 1/152,232 · joint denominator

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.Arg13Pro
Coding: c.38G>C
MANE Select: NM_005732
Type: single nucleotide variant
Location: chr5:132557362 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 6 PDB
Residue 13: a binding site

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.Arg13= Likely benign ★★ same residue
RAD50 p.Arg13Gln 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
RAD50 c.129+1G>A 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-arg13pro (accessed [today's date]).

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