Is RAD51D p.Arg232Pro (c.695G>C) pathogenic?

RAD51D p.Arg232Pro (c.695G>C) is classified Uncertain significance in RAD51D (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-08-22). AlphaMissense: likely pathogenic (0.919); Very rare (popmax 0.00221%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 4.

How common is RAD51D p.Arg232Pro (c.695G>C) in the general population?

RAD51D p.Arg232Pro (c.695G>C) is very rare (popmax 0.00221%, sas) (gnomAD).

What do computational predictors say about RAD51D p.Arg232Pro (c.695G>C)?

AlphaMissense predicts likely pathogenic (score 0.919) — an in-silico prediction, not a clinical call.

RAD51D p.Arg232Pro

Q: What condition is associated with RAD51D p.Arg232Pro (c.695G>C)?

RAD51D p.Arg232Pro (c.695G>C) is associated with breast-ovarian cancer, familial, susceptibility to, 4, hereditary neoplastic syndrome (ClinVar).

c.695G>C · rs28363283 · VCV581983

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.919 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

breast-ovarian cancer, familial, susceptibility to, 4

Computational evidence

Protein change
AlphaMissense	0.919	likely pathogenic · top 9% in RAD51D
REVEL	0.363	indeterminate
SaProt	LLR -15.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.51	GERP -2.1
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.24 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% South Asian · 2/90,476 alleles

Filtering AF 0.000367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000248% 4/1,611,706 alleles · very rare exomes 4/1,459,464 · genomes 0/152,242 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00221%	45,238
European (non-Finnish)	0.00017%	589,553

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.Arg232Pro
Coding: c.695G>C
MANE Select: NM_002878
dbSNP: rs28363283
Type: single nucleotide variant
Location: chr17:35103297 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 232: a UniProt-annotated variant site (in); 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 neoplastic syndrome

Similar variants

RAD51D p.Arg232Gln Benign/Likely benign ★★ same residue
RAD51D p.Arg232Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
RAD51D p.Arg232_Arg239delinsTer Pathogenic ★ same residue
RAD51D p.Arg232Ter Pathogenic ★ 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

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-arg232pro (accessed [today's date]).

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