Is RAD50 p.Leu802Phe (c.2404C>T) pathogenic?

RAD50 p.Leu802Phe (c.2404C>T) is classified Uncertain significance in RAD50 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-20). AlphaMissense: ambiguous (0.3433); Ultra-rare (popmax 0.0331%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Leu802Phe (c.2404C>T)?

RAD50 p.Leu802Phe (c.2404C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Leu802Phe (c.2404C>T) in the general population?

RAD50 p.Leu802Phe (c.2404C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about RAD50 p.Leu802Phe (c.2404C>T)?

AlphaMissense predicts ambiguous (score 0.3433) — an in-silico prediction, not a clinical call.

RAD50 p.Leu802Phe

c.2404C>T · rs752214704 · VCV1790775

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3433 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3433	ambiguous
REVEL	0.106	moderately benign-leaning
SaProt	LLR -10.44	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 3.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 0.00013 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.0331% Middle Eastern · 2/6,038 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.000207% 3/1,447,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,019
European (non-Finnish)	8.56e-05%	1,167,722

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.Leu802Phe
Coding: c.2404C>T
MANE Select: NM_005732
dbSNP: rs752214704
Type: single nucleotide variant
Location: chr5:132603926 (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.Leu802Ile 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
RAD50 c.129+1G>T 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-leu802phe (accessed [today's date]).

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