Is RAD51C p.Phe17= (c.51C>T) pathogenic?

RAD51C p.Phe17= (c.51C>T) is classified Benign/Likely benign in RAD51C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-06-16). Very rare (popmax 8.47e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51C p.Phe17= (c.51C>T)?

RAD51C p.Phe17= (c.51C>T) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group O, breast-ovarian cancer, familial, susceptibility to, 3 (ClinVar).

How common is RAD51C p.Phe17= (c.51C>T) in the general population?

RAD51C p.Phe17= (c.51C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

RAD51C p.Phe17=

c.51C>T · rs1598448876 · VCV761485

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 -4.4	GERP -3
Overall
CADD	7.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,056 alleles

Overall 6.19e-05% 1/1,614,248 alleles · very rare exomes 1/1,461,888 · genomes 0/152,360 · 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.Phe17=
Coding: c.51C>T
MANE Select: NM_058216
dbSNP: rs1598448876
Type: single nucleotide variant
Location: chr17:58692694 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.23 · 17 PDB
Residue 17: the 'required for holliday junction resolution activity' region

Full RAD51C 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: Fanconi anemia complementation group O breast-ovarian cancer, familial, susceptibility to, 3

Similar variants

RAD51C p.Phe17Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C p.Phe17Leu Uncertain significance ★ ⚠ same residue
RAD51C p.Phe17Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51C p.Phe17Tyr Likely benign ★ ⚠ same residue
RAD51C p.Phe17fs Pathogenic/Likely pathogenic ★★ 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

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-phe17 (accessed [today's date]).

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