Is RAD51D p.Pro65Ser (c.193C>T) pathogenic?

RAD51D p.Pro65Ser (c.193C>T) is classified Uncertain significance in RAD51D (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-23). AlphaMissense: likely pathogenic (0.5726); Very rare (popmax 0.00167%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Pro65Ser (c.193C>T)?

RAD51D p.Pro65Ser (c.193C>T) is associated with hereditary neoplastic syndrome, breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How common is RAD51D p.Pro65Ser (c.193C>T) in the general population?

RAD51D p.Pro65Ser (c.193C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about RAD51D p.Pro65Ser (c.193C>T)?

AlphaMissense predicts likely pathogenic (score 0.5726) — an in-silico prediction, not a clinical call.

RAD51D p.Pro65Ser

c.193C>T · rs766692136 · VCV921725

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.5726 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.5726	likely pathogenic
REVEL	0.334	indeterminate
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 19 kb · p 0.24 · regional, not allelic
Overall
CADD	26.2	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 0.00167% Admixed American · 1/60,000 alleles

Overall 0.000124% 2/1,614,078 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,000
African / African-American	0.00133%	74,938

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.Pro65Ser
Coding: c.193C>T
MANE Select: NM_002878
dbSNP: rs766692136
Type: single nucleotide variant
Location: chr17:35118571 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 65: the 'preferentially binds ssdna' region

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.Pro65Ala Uncertain significance ★★ ⚠ same residue
RAD51D p.Pro65Arg Uncertain significance ★★ ⚠ same residue
RAD51D p.Pro65Leu Uncertain significance ★★ same residue
RAD51D p.Pro65_Val66insTer 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-pro65ser (accessed [today's date]).

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