Is RAD51D p.Ala293= (c.879G>A) pathogenic?

RAD51D p.Ala293= (c.879G>A) is classified Conflicting classifications of pathogenicity in RAD51D (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-01-02). Ultra-rare (popmax 0.0183%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Ala293= (c.879G>A)?

RAD51D p.Ala293= (c.879G>A) is associated with hereditary neoplastic syndrome, breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How common is RAD51D p.Ala293= (c.879G>A) in the general population?

RAD51D p.Ala293= (c.879G>A) is ultra-rare (popmax 0.0183%, nfe) (gnomAD).

RAD51D p.Ala293=

c.879G>A · rs368209468 · VCV186175

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, 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 -7.9	GERP -3.1
Overall
CADD	0.472	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% European (non-Finnish) · 216/1,180,040 alleles

Filtering AF 0.0163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.0139% 224/1,614,012 alleles · ultra-rare exomes 217/1,461,870 · genomes 7/152,142 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0183%	5,463
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.005%	20,000
East Asian	0.00223%	44,876

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.Ala293=
Coding: c.879G>A
MANE Select: NM_002878
dbSNP: rs368209468
Type: single nucleotide variant
Location: chr17:35101225 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 293: a β-strand

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.Ala293Thr Uncertain significance ★★ ⚠ same residue
RAD51D p.Ala293Glu Uncertain significance ★ ⚠ same residue
RAD51D p.Ala293Val 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

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-ala293 (accessed [today's date]).

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