Is BRCA2 p.Ser2414= (c.7242A>G) pathogenic?

BRCA2 p.Ser2414= (c.7242A>G) is classified Benign in BRCA2 (ClinVar, Expert panel, 31 submitters; last evaluated 2015-01-12). Common (popmax 42.8%, 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.Ser2414= (c.7242A>G)?

BRCA2 p.Ser2414= (c.7242A>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.Ser2414=

Q: How common is BRCA2 p.Ser2414= (c.7242A>G) in the general population?

BRCA2 p.Ser2414= (c.7242A>G) is common (popmax 42.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7242A>G · rs1799955 · VCV126133

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 31 submitters

gnomAD v4.1

Common

common (popmax 42.8%, 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 0.23	GERP -4.3
Overall
CADD	5.715	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.8% East Asian · 19,206/44,826 alleles

Filtering AF 42.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.1%

Overall 22.2% 357,391/1,613,446 alleles · common exomes 323,719/1,461,306 · genomes 33,672/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	42.8%	2
Finnishnot grpmax-eligible	23.3%	4
Remaining individualsnot grpmax-eligible	22.3%	4
South Asian	22%	5
European (non-Finnish)	21.6%	5
African / African-American	21.5%	5
Ashkenazi Jewishnot grpmax-eligible	21.2%	5
Middle Eastern	20.4%	5
Admixed American	18.1%	6
Amishnot grpmax-eligible	12.7%	8

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.Ser2414=
Coding: c.7242A>G
MANE Select: NM_000059
dbSNP: rs1799955
Type: single nucleotide variant
Location: chr13:32355095 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 2414: the 'interaction with fancd2' region

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.Ser2414Ala Uncertain significance ★★ same residue
BRCA2 p.Ser2414Ter Pathogenic ★ same residue
BRCA2 p.Ser2414Leu Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ser2414Pro Uncertain significance ★ 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-ser2414 (accessed [today's date]).

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