Is RAD51D p.Val28fs (c.81del) pathogenic?

RAD51D p.Val28fs (c.81del) is classified Pathogenic in RAD51D (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-23). Very rare (popmax 0.000254%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 4.

What condition is associated with RAD51D p.Val28fs (c.81del)?

RAD51D p.Val28fs (c.81del) is associated with breast-ovarian cancer, familial, susceptibility to, 4, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is RAD51D p.Val28fs (c.81del) in the general population?

RAD51D p.Val28fs (c.81del) is very rare (popmax 0.000254%, nfe) (gnomAD).

RAD51D p.Val28fs

c.81del · rs1064793952 · VCV419558

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

breast-ovarian cancer, familial, susceptibility to, 4

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	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,924 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,459,462 alleles · very rare

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: RAD51D
Protein: p.Val28fs
Coding: c.81del
MANE Select: NM_002878
dbSNP: rs1064793952
Type: Deletion
Location: chr17:35119533 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 28: the 'preferentially binds ssdna' region; an α-helix

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

Disease context

breast-ovarian cancer, familial, susceptibility to, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

Similar variants

RAD51D p.Val28Met Uncertain significance ★★ ⚠ same residue
RAD51D p.Val28Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51D c.131_144+24del Pathogenic/Likely pathogenic ★★ same condition
RAD51D p.Ala122fs Pathogenic/Likely pathogenic ★★ same condition
RAD51D p.Ala163fs Pathogenic ★★ same condition
RAD51D p.Ala296fs Pathogenic/Likely pathogenic ★★ same condition
RAD51D p.Arg145fs Pathogenic ★★ same condition
RAD51D p.Arg255fs 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/rad51d-p-val28fs (accessed [today's date]).

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