Is RAD51D p.Ser299fs (c.896_*505del597insT) pathogenic?

RAD51D p.Ser299fs (c.896505del597insT) is classified Pathogenic in RAD51D (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-12). Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with RAD51D p.Ser299fs (c.896_*505del597insT)?

RAD51D p.Ser299fs (c.896_*505del597insT) is associated with hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

RAD51D p.Ser299fs

c.896_*505del597insT · VCV1713232

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.2	GERP 0.24, phastCons 0.28

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: RAD51D
Protein: p.Ser299fs
Coding: c.896_*505del597insT
MANE Select: NM_002878
Type: Indel
Location: chr17:35100448 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 299: a β-strand

Full RAD51D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: breast-ovarian cancer, familial, susceptibility to, 4

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

RAD51D p.Ser299_Ter329delinsXaa Likely pathogenic ★ same residue
RAD51D p.Gly217_Gln219delinsTer Pathogenic ★★ same condition
RAD51D p.Leu8fs Pathogenic ★★ same condition
RAD51D p.Ser299Phe Uncertain significance ★★ ⚠ same residue
RAD51D c.144+1_144+11delinsCC Likely pathogenic ★ same condition
RAD51D c.346-2delinsCG Likely pathogenic ★ same condition
RAD51D p.Cys9Ter Pathogenic ★ same condition
RAD51D p.Val170fs 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/rad51d-p-ser299fs (accessed [today's date]).

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