Is BRCA2 p.Gln147Arg (c.440A>G) pathogenic?

BRCA2 p.Gln147Arg (c.440A>G) is classified Benign in BRCA2 (ClinVar, Expert panel, 27 submitters; last evaluated 2019-06-18). AlphaMissense: likely benign (0.0714); Rare (popmax 0.116%, eas); Associated with breast-ovarian cancer, familial, susceptibility to, 2.

What condition is associated with BRCA2 p.Gln147Arg (c.440A>G)?

BRCA2 p.Gln147Arg (c.440A>G) is associated with breast-ovarian cancer, familial, susceptibility to, 2, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Gln147Arg (c.440A>G) in the general population?

BRCA2 p.Gln147Arg (c.440A>G) is rare (popmax 0.116%, eas) (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.

What do computational predictors say about BRCA2 p.Gln147Arg (c.440A>G)?

AlphaMissense predicts likely benign (score 0.0714) — an in-silico prediction, not a clinical call.

BRCA2 p.Gln147Arg

c.440A>G · rs80358674 · VCV51644

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 27 submitters

AlphaMissense

likely benign

0.0714 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

Conditions

breast-ovarian cancer, familial, susceptibility to, 2

Computational evidence

Protein change
AlphaMissense	0.0714	likely benign
REVEL	0.338	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -4.5
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	0.166	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% East Asian · 52/44,762 alleles

Filtering AF 0.0909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.082%

Overall 0.0064% 103/1,610,194 alleles · rare exomes 88/1,457,950 · genomes 15/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	861
Remaining individualsnot grpmax-eligible	0.0642%	1,557
Admixed American	0.005%	19,993
African / African-American	0.00401%	24,939
South Asian	0.0011%	90,810
European (non-Finnish)	0.000339%	294,579

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.Gln147Arg
Coding: c.440A>G
MANE Select: NM_000059
dbSNP: rs80358674
Type: single nucleotide variant
Location: chr13:32326115 (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 breast cancer ovarian cancer malignant pancreatic neoplasm 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.Gln147Ter Pathogenic ★★★ same residue
BRCA2 p.Gln147= Likely benign ★★★ same residue
BRCA2 p.Gln147His Uncertain significance ★★ ⚠ same residue
BRCA2 p.Gln147Leu Uncertain significance ★★ ⚠ same residue
BRCA2 p.Gln147fs Pathogenic ★★★ 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

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-gln147arg (accessed [today's date]).

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