Is RAD51C p.Phe99= (c.297C>T) pathogenic?

RAD51C p.Phe99= (c.297C>T) is classified Likely benign in RAD51C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-15). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51C p.Phe99= (c.297C>T)?

RAD51C p.Phe99= (c.297C>T) is associated with hereditary neoplastic syndrome, Fanconi anemia complementation group O (ClinVar).

How common is RAD51C p.Phe99= (c.297C>T) in the general population?

RAD51C p.Phe99= (c.297C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

RAD51C p.Phe99=

c.297C>T · rs2143723622 · VCV1798374

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

hereditary neoplastic syndrome

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 2.7	GERP -0.35, phastCons 1
Overall
CADD	12.43	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,024 alleles

Overall 6.2e-05% 1/1,614,108 alleles · very rare exomes 1/1,461,872 · genomes 0/152,236 · 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.Phe99=
Coding: c.297C>T
MANE Select: NM_058216
dbSNP: rs2143723622
Type: single nucleotide variant
Location: chr17:58695082 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.23 · 17 PDB
Residue 99: the 'required for holliday junction resolution activity' region; the 'interaction with rad51b, rad51d and xrcc3' 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

Similar variants

RAD51C p.Phe99Ser Uncertain significance ★ ⚠ same residue
RAD51C p.Phe99Leu Benign ★ ⚠ same residue
RAD51C p.Phe99fs 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
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-phe99 (accessed [today's date]).

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