Is BRCA2 p.Gly173Arg (c.517G>C) pathogenic?

BRCA2 p.Gly173Arg (c.517G>C) is classified Pathogenic/Likely pathogenic in BRCA2 (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-05-18). AlphaMissense: likely benign (0.333); Very rare (popmax 8.55e-05%, nfe); Associated with Inherited breast cancer and ovarian cancer.

What condition is associated with BRCA2 p.Gly173Arg (c.517G>C)?

BRCA2 p.Gly173Arg (c.517G>C) is associated with Inherited breast cancer and ovarian cancer, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA2 p.Gly173Arg (c.517G>C) in the general population?

BRCA2 p.Gly173Arg (c.517G>C) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Gly173Arg (c.517G>C)?

AlphaMissense predicts likely benign (score 0.333) — an in-silico prediction, not a clinical call.

BRCA2 p.Gly173Arg

c.517G>C · rs397507768 · VCV182177

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

AlphaMissense

likely benign

0.333 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inherited breast cancer and ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.333	likely benign ⚠ discordant with ClinVar
REVEL	0.09	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	Δ0.41	acceptor loss at this position · masked 0 · deltas
Pangolin	Δ0.35	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.6	GERP 0.55, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,168,988 alleles

Overall 6.9e-05% 1/1,449,710 alleles · very rare

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.Gly173Arg
Coding: c.517G>C
MANE Select: NM_000059
dbSNP: rs397507768
Type: single nucleotide variant
Location: chr13:32326499 (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

Inherited breast cancer and ovarian cancer

Also linked: hereditary breast ovarian cancer syndrome breast cancer breast-ovarian cancer, familial, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRCA2 p.Gly173Asp Uncertain significance ★★ ⚠ same residue
BRCA2 p.Gly173Ser Uncertain significance ★★ ⚠ same residue
BRCA2 p.Gly173Ala Uncertain significance ★ ⚠ same residue
BRCA2 p.Gly173Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Gly173Val Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Gly173Valfs Pathogenic ★★★ same residue
BRCA2 p.Gly173fs Pathogenic ★★ same residue
BRCA2 c.316+1G>T 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-gly173arg (accessed [today's date]).

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