Is RAD50 p.Val72Phe (c.214G>T) pathogenic?

RAD50 p.Val72Phe (c.214G>T) is classified Uncertain significance in RAD50 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-16). AlphaMissense: ambiguous (0.4835); Very rare (popmax 8.64e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Val72Phe (c.214G>T)?

RAD50 p.Val72Phe (c.214G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Val72Phe (c.214G>T) in the general population?

RAD50 p.Val72Phe (c.214G>T) is very rare (popmax 8.64e-05%, nfe) (gnomAD).

What do computational predictors say about RAD50 p.Val72Phe (c.214G>T)?

AlphaMissense predicts ambiguous (score 0.4835) — an in-silico prediction, not a clinical call.

RAD50 p.Val72Phe

c.214G>T · rs118029772 · VCV966493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4835 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.64e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.4835	ambiguous
REVEL	0.174	moderately benign-leaning
SaProt	LLR -7.32	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 2.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 38 kb · p 0.02 · regional, not allelic
Overall
CADD	27.5	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 8.64e-05% European (non-Finnish) · 1/1,157,338 alleles

Overall 6.29e-05% 1/1,589,120 alleles · very rare exomes 1/1,436,918 · genomes 0/152,202 · 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.Val72Phe
Coding: c.214G>T
MANE Select: NM_005732
dbSNP: rs118029772
Type: single nucleotide variant
Location: chr5:132575777 (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.Val72Ile 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-val72phe (accessed [today's date]).

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