Is RAD51D p.Ser78= (c.234C>T) pathogenic?

RAD51D p.Ser78= (c.234C>T) is classified Benign/Likely benign in RAD51D (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Ser78= (c.234C>T)?

RAD51D p.Ser78= (c.234C>T) is associated with hereditary neoplastic syndrome, breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

RAD51D p.Ser78=

Q: How common is RAD51D p.Ser78= (c.234C>T) in the general population?

RAD51D p.Ser78= (c.234C>T) is common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.234C>T · rs9901455 · VCV183785

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 30.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary neoplastic syndrome

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 5.8	GERP 1.4, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.1% African / African-American · 22,594/74,972 alleles

Filtering AF 29.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 29.7%

Overall 9.71% 156,705/1,613,868 alleles · common exomes 133,000/1,461,720 · genomes 23,705/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.1%	3
East Asian	25.7%	4
Ashkenazi Jewishnot grpmax-eligible	14.4%	7
Middle Eastern	13%	8
Admixed American	11.2%	9
Finnishnot grpmax-eligible	11.1%	9
Remaining individualsnot grpmax-eligible	10.5%	9
South Asian	8.65%	12
European (non-Finnish)	7.56%	13
Amishnot grpmax-eligible	0.658%	152

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.Ser78=
Coding: c.234C>T
MANE Select: NM_002878
dbSNP: rs9901455
Type: single nucleotide variant
Location: chr17:35118530 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 78: the 'preferentially binds ssdna' region; an α-helix

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.Ser78Phe 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
RAD51D c.481-1G>A 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-ser78 (accessed [today's date]).

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