Is RAD51C p.Arg2= (c.6C>T) pathogenic?

RAD51C p.Arg2= (c.6C>T) is classified Benign/Likely benign in RAD51C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-13). Very rare (popmax 0.000169%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 3.

What condition is associated with RAD51C p.Arg2= (c.6C>T)?

RAD51C p.Arg2= (c.6C>T) is associated with breast-ovarian cancer, familial, susceptibility to, 3, Fanconi anemia complementation group O, hereditary neoplastic syndrome (ClinVar).

How common is RAD51C p.Arg2= (c.6C>T) in the general population?

RAD51C p.Arg2= (c.6C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

RAD51C p.Arg2=

c.6C>T · rs1334508786 · VCV763787

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

breast-ovarian cancer, familial, susceptibility to, 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2	GERP -4.1
Overall
CADD	8.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,004 alleles · very rare exomes 1/1,461,798 · genomes 1/152,206 · 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: RAD51C
Protein: p.Arg2=
Coding: c.6C>T
MANE Select: NM_058216
dbSNP: rs1334508786
Type: single nucleotide variant
Location: chr17:58692649 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.23 · 17 PDB
Residue 2: the 'required for holliday junction resolution activity' region

Full RAD51C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group O hereditary neoplastic syndrome

Similar variants

RAD51C p.Arg2Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C p.Arg2Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C p.Arg2His Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C c.145+1G>A Pathogenic/Likely pathogenic ★★ same condition
RAD51C c.145+1G>T Pathogenic/Likely pathogenic ★★ same condition
RAD51C c.146-1G>A Likely pathogenic ★★ same condition
RAD51C c.404+1G>A Likely pathogenic ★★ same condition
RAD51C c.404+2T>C Pathogenic/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/rad51c-p-arg2 (accessed [today's date]).

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