Is RAD51D p.Pro272= (c.816C>T) pathogenic?

RAD51D p.Pro272= (c.816C>T) is classified Benign/Likely benign in RAD51D (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-15). Very rare (popmax 0.0022%, sas); Associated with breast-ovarian cancer, familial, susceptibility to, 4.

What condition is associated with RAD51D p.Pro272= (c.816C>T)?

RAD51D p.Pro272= (c.816C>T) is associated with breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How common is RAD51D p.Pro272= (c.816C>T) in the general population?

RAD51D p.Pro272= (c.816C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

RAD51D p.Pro272=

c.816C>T · rs565863781 · VCV2812403

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.6	GERP -3.1, phastCons 1
Overall
CADD	8.124	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,080 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000124% 2/1,614,098 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.Pro272=
Coding: c.816C>T
MANE Select: NM_002878
dbSNP: rs565863781
Type: single nucleotide variant
Location: chr17:35101288 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB

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

Similar variants

RAD51D p.Pro272Ser Uncertain significance ★★ ⚠ same residue
RAD51D p.Pro272_Leu278delinsLeuGlyPheSer Uncertain significance ★ 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-pro272 (accessed [today's date]).

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