Is BRCA2 p.Ala39Phe (c.115_116delinsTT) pathogenic?

BRCA2 p.Ala39Phe (c.115116delinsTT) is classified Uncertain significance in BRCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-10). Absent from gnomAD; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA2 p.Ala39Phe (c.115_116delinsTT)?

BRCA2 p.Ala39Phe (c.115_116delinsTT) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ala39Phe (c.115_116delinsTT) in the general population?

BRCA2 p.Ala39Phe (c.115_116delinsTT) is absent from gnomAD (gnomAD).

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.Ala39Phe

c.115_116delinsTT · rs2548511177 · VCV2694639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.5	GERP 2.3, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA2
Protein: p.Ala39Phe
Coding: c.115_116delinsTT
MANE Select: NM_000059
dbSNP: rs2548511177
Type: Indel
Location: chr13:32319124 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 39: the 'disordered' region; the 'interaction with palb2' region

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

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ala39fs Pathogenic ★★★ same residue
BRCA2 p.Ala39Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala39= Likely benign ★ same residue
BRCA2 c.8954-1_8955delinsAA Pathogenic ★★★ same condition
BRCA2 p.Arg1160_Asp1161delinsTer Pathogenic ★★★ same condition
BRCA2 p.Arg2799fs Pathogenic ★★★ same condition
BRCA2 p.Glu1608fs Pathogenic ★★★ same condition
BRCA2 p.Ile1705fs 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-ala39phe (accessed [today's date]).

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