Is BRCA2 p.Ala622Ter (c.1864_1865delinsTA) pathogenic?

BRCA2 p.Ala622Ter (c.18641865delinsTA) is classified Pathogenic/Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-30). Absent from gnomAD; Associated with hereditary breast carcinoma.

What condition is associated with BRCA2 p.Ala622Ter (c.1864_1865delinsTA)?

BRCA2 p.Ala622Ter (c.1864_1865delinsTA) is associated with hereditary breast carcinoma, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA2 p.Ala622Ter (c.1864_1865delinsTA) in the general population?

BRCA2 p.Ala622Ter (c.1864_1865delinsTA) is absent from gnomAD (gnomAD).

How is Hereditary breast cancer inherited?

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

BRCA2 p.Ala622Ter

c.1864_1865delinsTA · rs2072424360 · VCV968680

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 0.39, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Ala622Ter
Coding: c.1864_1865delinsTA
MANE Select: NM_000059
dbSNP: rs2072424360
Type: Indel
Location: chr13:32333342 (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

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

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRCA2 p.Ala622Val Benign ★★★ same residue
BRCA2 p.Ala622Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala622Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala622Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala622= Likely benign ★ same residue
BRCA2 c.1587delinsCA Pathogenic ★★★ same condition
BRCA2 c.8954-1_8955delinsAA Pathogenic ★★★ same condition
BRCA2 p.Arg1160_Asp1161delinsTer 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-ala622ter (accessed [today's date]).

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