Is RAD50 p.Pro30Ser (c.88C>T) pathogenic?

RAD50 p.Pro30Ser (c.88C>T) is classified Uncertain significance in RAD50 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-27). AlphaMissense: likely pathogenic (0.9429); Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Pro30Ser (c.88C>T)?

RAD50 p.Pro30Ser (c.88C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Pro30Ser (c.88C>T) in the general population?

RAD50 p.Pro30Ser (c.88C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about RAD50 p.Pro30Ser (c.88C>T)?

AlphaMissense predicts likely pathogenic (score 0.9429) — an in-silico prediction, not a clinical call.

RAD50 p.Pro30Ser

c.88C>T · rs1321131254 · VCV822806

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9429	likely pathogenic
REVEL	0.473	indeterminate
SaProt	LLR -13.69	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 3.4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 38 kb · p 0.02 · regional, not allelic
Overall
CADD	28.2	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 0.00223% East Asian · 1/44,888 alleles

Overall 0.000186% 3/1,614,164 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,888
Admixed American	0.00167%	60,030
South Asian	0.0011%	91,090

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.Pro30Ser
Coding: c.88C>T
MANE Select: NM_005732
dbSNP: rs1321131254
Type: single nucleotide variant
Location: chr5:132557412 (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.Pro30Leu Uncertain significance ★★ ⚠ same residue
RAD50 p.Pro30= Likely benign ★★ same residue
RAD50 p.Pro30Arg Uncertain significance ★ ⚠ same residue
RAD50 p.Pro30Thr 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-pro30ser (accessed [today's date]).

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