Is BRCA2 p.Ser455= (c.1365A>G) pathogenic?

BRCA2 p.Ser455= (c.1365A>G) is classified Benign in BRCA2 (ClinVar, Expert panel, 32 submitters; last evaluated 2015-01-12). Common (popmax 11.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Ser455= (c.1365A>G)?

BRCA2 p.Ser455= (c.1365A>G) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, Fanconi anemia complementation group D1 (ClinVar).

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

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

BRCA2 p.Ser455=

Q: How common is BRCA2 p.Ser455= (c.1365A>G) in the general population?

BRCA2 p.Ser455= (c.1365A>G) is common (popmax 11.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1365A>G · rs1801439 · VCV125943

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 32 submitters

gnomAD v4.1

Common

common (popmax 11.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.6	GERP -1.6, phastCons 0.71
Overall
CADD	6.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.7% East Asian · 5,236/44,860 alleles

Filtering AF 11.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.3%

Overall 4.2% 67,606/1,611,544 alleles · common exomes 61,373/1,459,224 · genomes 6,233/152,320 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	11.7%	9
South Asian	11.5%	9
Admixed American	8.05%	12
Middle Eastern	5.43%	18
Remaining individualsnot grpmax-eligible	4.57%	22
Ashkenazi Jewishnot grpmax-eligible	4.15%	24
European (non-Finnish)	3.42%	29
Amishnot grpmax-eligible	2.63%	38
African / African-American	2.09%	48
Finnishnot grpmax-eligible	1.51%	66

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: BRCA2
Protein: p.Ser455=
Coding: c.1365A>G
MANE Select: NM_000059
dbSNP: rs1801439
Type: single nucleotide variant
Location: chr13:32332843 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)

Full BRCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

breast-ovarian cancer, familial, susceptibility to, 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome Fanconi anemia complementation group D1 hereditary neoplastic syndrome hereditary breast carcinoma

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ser455Ter Pathogenic ★★ same residue
BRCA2 p.Ser455Pro Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser455fs Pathogenic ★★★ same residue
BRCA2 p.Ser455Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>C Pathogenic ★★★ same condition
BRCA2 c.316+5G>A Pathogenic ★★★ same condition
BRCA2 c.316+5G>C 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/brca2-p-ser455 (accessed [today's date]).

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