Is RAD51D p.Ser196Phe (c.587C>T) pathogenic?

RAD51D p.Ser196Phe (c.587C>T) is classified Uncertain significance in RAD51D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely benign (0.1088); Absent from gnomAD v4.1; Associated with breast-ovarian cancer, familial, susceptibility to, 4.

What condition is associated with RAD51D p.Ser196Phe (c.587C>T)?

RAD51D p.Ser196Phe (c.587C>T) is associated with breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How common is RAD51D p.Ser196Phe (c.587C>T) in the general population?

RAD51D p.Ser196Phe (c.587C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD51D p.Ser196Phe (c.587C>T)?

AlphaMissense predicts likely benign (score 0.1088) — an in-silico prediction, not a clinical call.

RAD51D p.Ser196Phe

c.587C>T · rs2142421076 · VCV2095833

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1088 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

breast-ovarian cancer, familial, susceptibility to, 4

Computational evidence

Protein change
AlphaMissense	0.1088	likely benign
REVEL	0.12	moderately benign-leaning
SaProt	LLR -10.40	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.38	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.24 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAD51D
Protein: p.Ser196Phe
Coding: c.587C>T
MANE Select: NM_002878
dbSNP: rs2142421076
Type: single nucleotide variant
Location: chr17:35103534 (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 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
RAD51D c.481-1G>A Likely pathogenic ★★ same condition
RAD51D c.576+1G>A 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-ser196phe (accessed [today's date]).

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