Is RAD50 p.Ala657Asp (c.1970C>A) pathogenic?

RAD50 p.Ala657Asp (c.1970C>A) is classified Uncertain significance in RAD50 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-18). AlphaMissense: likely pathogenic (0.9926); No allele count reported in gnomAD v4.1 (AN 1,594,880); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Ala657Asp (c.1970C>A)?

RAD50 p.Ala657Asp (c.1970C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is RAD50 p.Ala657Asp (c.1970C>A) in the general population?

RAD50 p.Ala657Asp (c.1970C>A) is no allele count reported in gnomAD v4.1 (AN 1,594,880) (gnomAD).

What do computational predictors say about RAD50 p.Ala657Asp (c.1970C>A)?

AlphaMissense predicts likely pathogenic (score 0.9926) — an in-silico prediction, not a clinical call.

RAD50 p.Ala657Asp

c.1970C>A · rs1750775187 · VCV1390324

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9926 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,594,880)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9926	likely pathogenic · top 5% in RAD50
REVEL	0.377	indeterminate
SaProt	LLR -3.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 38 kb · p 0.02 · regional, not allelic
Overall
CADD	29.3	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

No allele count reported in gnomAD v4.1 (AN 1,594,880). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RAD50
Protein: p.Ala657Asp
Coding: c.1970C>A
MANE Select: NM_005732
dbSNP: rs1750775187
Type: single nucleotide variant
Location: chr5:132595573 (GRCh38)
Gene constraint: LOEUF 0.889 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 82.83 · 6 PDB
Residue 657: 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

Similar variants

RAD50 p.Ala657= Likely benign ★★ 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-ala657asp (accessed [today's date]).

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