Is BRCA2 p.Ala1891Val (c.5672C>T) pathogenic?

BRCA2 p.Ala1891Val (c.5672C>T) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.128); Very rare (popmax 0.00134%, afr); Associated with Fanconi anemia complementation group D1.

What condition is associated with BRCA2 p.Ala1891Val (c.5672C>T)?

BRCA2 p.Ala1891Val (c.5672C>T) is associated with Fanconi anemia complementation group D1, hereditary breast ovarian cancer syndrome, medulloblastoma (ClinVar).

How common is BRCA2 p.Ala1891Val (c.5672C>T) in the general population?

BRCA2 p.Ala1891Val (c.5672C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about BRCA2 p.Ala1891Val (c.5672C>T)?

AlphaMissense predicts likely benign (score 0.128) — an in-silico prediction, not a clinical call.

BRCA2 p.Ala1891Val

Q: How is Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.5672C>T · rs397507360 · VCV37987

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Fanconi anemia complementation group D1

Computational evidence

Protein change
AlphaMissense	0.128	likely benign
REVEL	0.276	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP 0.15
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	12.8	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 0.00134% African / African-American · 1/74,874 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.000682% 11/1,613,162 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,874
European (non-Finnish)	0.000848%	117,973

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.Ala1891Val
Coding: c.5672C>T
MANE Select: NM_000059
dbSNP: rs397507360
Type: single nucleotide variant
Location: chr13:32340027 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1891: the 'interaction with rad51' region

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

Disease context

Fanconi anemia complementation group D1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome medulloblastoma prostate cancer Wilms tumor 1 breast-ovarian cancer, familial, susceptibility to, 2 glioma susceptibility 3 pancreatic cancer, susceptibility to, 2 hereditary neoplastic syndrome hereditary breast carcinoma

For Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations (Orphanet):

Inheritance: Autosomal recessive

Similar variants

BRCA2 p.Ala1891Pro Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Ala1891Ser Uncertain significance ★ ⚠ same residue
BRCA2 p.Ala1891Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Ala1891= Likely benign ★ 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-ala1891val (accessed [today's date]).

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