Is RAD50 p.Ser142= (c.426T>C) pathogenic?

RAD50 p.Ser142= (c.426T>C) is classified Likely benign in RAD50 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-24). Ultra-rare (popmax 0.015%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD50 p.Ser142= (c.426T>C)?

RAD50 p.Ser142= (c.426T>C) is associated with hereditary neoplastic syndrome, Nijmegen breakage syndrome-like disorder (ClinVar).

How common is RAD50 p.Ser142= (c.426T>C) in the general population?

RAD50 p.Ser142= (c.426T>C) is ultra-rare (popmax 0.015%, nfe) (gnomAD).

RAD50 p.Ser142=

c.426T>C · rs368752746 · VCV184520

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, nfe)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 2.5, phastCons 1
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.015% European (non-Finnish) · 177/1,179,946 alleles

Filtering AF 0.0132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0113% 183/1,613,918 alleles · ultra-rare exomes 176/1,461,736 · genomes 7/152,182 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0064%	15,619
African / African-American	0.00267%	37,464

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.Ser142=
Coding: c.426T>C
MANE Select: NM_005732
dbSNP: rs368752746
Type: single nucleotide variant
Location: chr5:132579377 (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

Also linked: Nijmegen breakage syndrome-like disorder

Similar variants

RAD50 p.Ser142Asn Uncertain significance ★★ ⚠ same residue
RAD50 p.Ser142Gly Uncertain significance ★★ ⚠ same residue
RAD50 p.Ser142Ile Uncertain significance ★ ⚠ same residue
RAD50 p.Ser142fs Pathogenic ★ 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-ser142 (accessed [today's date]).

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