Is BRCA2 p.Ile505Val (c.1513A>G) pathogenic?

BRCA2 p.Ile505Val (c.1513A>G) is classified Likely benign in BRCA2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.0735); Very rare (popmax 0.00323%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ile505Val (c.1513A>G)?

BRCA2 p.Ile505Val (c.1513A>G) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Ile505Val (c.1513A>G) in the general population?

BRCA2 p.Ile505Val (c.1513A>G) is very rare (popmax 0.00323%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Ile505Val (c.1513A>G)?

AlphaMissense predicts likely benign (score 0.0735) — an in-silico prediction, not a clinical call.

BRCA2 p.Ile505Val

c.1513A>G · rs397507270 · VCV37744

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0735 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00323%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0735	likely benign
REVEL	0.195	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.93	GERP -4.5
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	0.007	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 0.00323% European (non-Finnish) · 38/1,174,942 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00211%

Overall 0.00251% 40/1,593,778 alleles · very rare exomes 36/1,441,560 · genomes 4/152,218 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00325%	30,754
European (non-Finnish)grpmax	0.00323%	30,920

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile505Val
Coding: c.1513A>G
MANE Select: NM_000059
dbSNP: rs397507270
Type: single nucleotide variant
Location: chr13:32332991 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 505: a UniProt-annotated variant site (in bc; benign)

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

Disease context

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

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

Similar variants

BRCA2 p.Ile505Thr Benign ★★★ same residue
BRCA2 p.Ile505Met Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ile505Leu Likely benign ★ same residue
BRCA2 p.Ile505fs 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
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-ile505val (accessed [today's date]).

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