Is RAD51D p.Val66= (c.198G>T) pathogenic?

RAD51D p.Val66= (c.198G>T) is classified Benign/Likely benign in RAD51D (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-02). Rare (popmax 0.348%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Val66= (c.198G>T)?

RAD51D p.Val66= (c.198G>T) is associated with hereditary neoplastic syndrome, breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How common is RAD51D p.Val66= (c.198G>T) in the general population?

RAD51D p.Val66= (c.198G>T) is rare (popmax 0.348%, eas) (gnomAD).

RAD51D p.Val66=

c.198G>T · rs200810304 · VCV184496

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.348%, eas)

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 1.9	GERP -0.7, phastCons 1
Overall
CADD	6.702	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.348% East Asian · 156/44,880 alleles

Filtering AF 0.303% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.286%

Overall 0.00973% 157/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.348%	288
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Val66=
Coding: c.198G>T
MANE Select: NM_002878
dbSNP: rs200810304
Type: single nucleotide variant
Location: chr17:35118566 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 66: the 'preferentially binds ssdna' region

Full RAD51D 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: breast-ovarian cancer, familial, susceptibility to, 4

Similar variants

RAD51D p.Val66Leu Uncertain significance ★ ⚠ same residue
RAD51D p.Val66Met Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51D c.144+1G>T Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.145-2A>G Likely pathogenic ★★ same condition
RAD51D c.264-1G>T Likely pathogenic ★★ same condition
RAD51D c.264-2A>G Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.346-1G>C Pathogenic/Likely pathogenic ★★ same condition
RAD51D c.480+1G>T 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-val66 (accessed [today's date]).

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