Is BRCA2 p.Ala1572Val (c.4715C>T) pathogenic?

BRCA2 p.Ala1572Val (c.4715C>T) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-28). AlphaMissense: likely benign (0.1053); Very rare (popmax 0.000678%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Ala1572Val (c.4715C>T)?

BRCA2 p.Ala1572Val (c.4715C>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Ala1572Val (c.4715C>T) in the general population?

BRCA2 p.Ala1572Val (c.4715C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about BRCA2 p.Ala1572Val (c.4715C>T)?

AlphaMissense predicts likely benign (score 0.1053) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala1572Val

c.4715C>T · rs2072511378 · VCV1742611

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1053 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1053	likely benign
REVEL	0.103	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -3.3, phastCons 0.006
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	1.508	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 0.000678% European (non-Finnish) · 8/1,179,894 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000547% 8/1,461,710 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.Ala1572Val
Coding: c.4715C>T
MANE Select: NM_000059
dbSNP: rs2072511378
Type: single nucleotide variant
Location: chr13:32339070 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1572: the 'interaction with rad51' region; the 'interaction with polh' region; the 'required for stimulation of polh dna polymerization activity' region

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

Similar variants

BRCA2 p.Ala1572Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala1572Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala1572Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala1572= Likely benign ★ same residue
BRCA2 p.Ala1572_Cys1573delinsGlyLysAspPro Uncertain significance ★★ same residue
BRCA2 p.Ala1572_Cys1573insTer Likely pathogenic ★ same residue
BRCA2 p.Ala1572fs Pathogenic ★ same residue
BRCA2 p.Ala1572_Cys1573delinsGlyLysAspSer Uncertain significance ★ same residue

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-ala1572val (accessed [today's date]).

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