Is RAD51D p.Ser62= (c.186G>A) pathogenic?

RAD51D p.Ser62= (c.186G>A) is classified Benign/Likely benign in RAD51D (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-20). Ultra-rare (popmax 0.0132%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with RAD51D p.Ser62= (c.186G>A)?

RAD51D p.Ser62= (c.186G>A) is associated with hereditary neoplastic syndrome, breast-ovarian cancer, familial, susceptibility to, 4 (ClinVar).

How common is RAD51D p.Ser62= (c.186G>A) in the general population?

RAD51D p.Ser62= (c.186G>A) is ultra-rare (popmax 0.0132%, sas) (gnomAD).

RAD51D p.Ser62=

c.186G>A · rs746984258 · VCV232539

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0132%, sas)

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 -11	GERP -2.8
Overall
CADD	4.698	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0132% South Asian · 12/91,088 alleles

Filtering AF 0.00751% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00593%

Overall 0.000991% 16/1,614,058 alleles · ultra-rare exomes 14/1,461,872 · genomes 2/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0132%	7,591
African / African-American	0.00133%	74,922
European (non-Finnish)	0.000254%	393,346

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.Ser62=
Coding: c.186G>A
MANE Select: NM_002878
dbSNP: rs746984258
Type: single nucleotide variant
Location: chr17:35118578 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 88.64 · 17 PDB
Residue 62: 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.Ser62Trp 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-ser62 (accessed [today's date]).

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