Is RAD51B p.Val9Met (c.25G>A) pathogenic?

RAD51B p.Val9Met (c.25G>A) is classified Conflicting classifications of pathogenicity in RAD51B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-07-08). AlphaMissense: likely benign (0.2134); Low-frequency (popmax 1.45%, afr); Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with RAD51B p.Val9Met (c.25G>A)?

RAD51B p.Val9Met (c.25G>A) is associated with hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is RAD51B p.Val9Met (c.25G>A) in the general population?

RAD51B p.Val9Met (c.25G>A) is low-frequency (popmax 1.45%, afr) (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about RAD51B p.Val9Met (c.25G>A)?

AlphaMissense predicts likely benign (score 0.2134) — an in-silico prediction, not a clinical call.

RAD51B p.Val9Met

c.25G>A · rs34583846 · VCV584553

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2134 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.45%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.2134	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 654 kb · p 0.17 · regional, not allelic
Overall
CADD	23.7	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

Grpmax group 1.45% African / African-American · 1,087/74,990 alleles

Filtering AF 1.38% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.35%

Overall 0.0752% 1,214/1,613,716 alleles · low-frequency exomes 580/1,461,528 · genomes 634/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.45%	69
Admixed American	0.0817%	1,224
Remaining individualsnot grpmax-eligible	0.0576%	1,736
Middle Eastern	0.033%	3,029
South Asian	0.0033%	30,337
European (non-Finnish)	0.00314%	31,888

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: RAD51B
Protein: p.Val9Met
Coding: c.25G>A
MANE Select: NM_133510
dbSNP: rs34583846
Type: single nucleotide variant
Location: chr14:67823568 (GRCh38)
Gene constraint: LOEUF 1.247 · pLI <0.01 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 5 PDB
Residue 9: the 'interaction with rad51c' region; an α-helix; a UniProt-annotated variant site (in)

Full RAD51B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

RAD51B p.Val9Gly Uncertain significance ★ ⚠ same residue
RAD51B p.Ala146Thr Uncertain significance ★★ ⚠ same condition
RAD51B p.Ala268Pro Uncertain significance ★★ ⚠ same condition
RAD51B p.Arg47Ter Uncertain significance ★★ same condition
RAD51B p.Pro326Ala Uncertain significance ★★ same condition
RAD51B p.Tyr68Cys Uncertain significance ★★ ⚠ same condition
RAD51B c.199-21C>T Benign ★★ same condition
RAD51B c.199-33G>T Benign ★★ 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/rad51b-p-val9met (accessed [today's date]).

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