Is BRCA1 p.Asn1132Asp (c.3394A>G) pathogenic?

BRCA1 p.Asn1132Asp (c.3394A>G) is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-13). AlphaMissense: likely benign (0.1001); Ultra-rare (popmax 0.0173%, afr); Associated with pancreatic cancer, susceptibility to, 4.

What condition is associated with BRCA1 p.Asn1132Asp (c.3394A>G)?

BRCA1 p.Asn1132Asp (c.3394A>G) is associated with pancreatic cancer, susceptibility to, 4, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Asn1132Asp (c.3394A>G) in the general population?

BRCA1 p.Asn1132Asp (c.3394A>G) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

What do computational predictors say about BRCA1 p.Asn1132Asp (c.3394A>G)?

AlphaMissense predicts likely benign (score 0.1001) — an in-silico prediction, not a clinical call.

BRCA1 p.Asn1132Asp

c.3394A>G · rs530464947 · VCV183852

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.1001 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pancreatic cancer, susceptibility to, 4

Computational evidence

Protein change
AlphaMissense	0.1001	likely benign
REVEL	0.259	benign-leaning
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.96	GERP -2.1, phastCons 0.66
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	15.35	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 0.0173% African / African-American · 13/75,062 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.000806% 13/1,613,748 alleles · ultra-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: BRCA1
Protein: p.Asn1132Asp
Coding: c.3394A>G
MANE Select: NM_007294
dbSNP: rs530464947
Type: single nucleotide variant
Location: chr17:43092137 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1132: a UniProt-annotated variant site (in fancs)

Full BRCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pancreatic cancer, susceptibility to, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome Fanconi anemia, complementation group S

Similar variants

BRCA1 p.Asn1132= Likely benign ★★★ same residue
BRCA1 p.Asn1132_Leu1133insTer Pathogenic ★★★ same residue
BRCA1 p.Asn1132fs Pathogenic ★★★ same residue
BRCA1 p.Asn1132_Leu1133del Uncertain significance ★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T Pathogenic ★★★ same condition
BRCA1 c.212+1G>A Pathogenic ★★★ same condition
BRCA1 c.212+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/brca1-p-asn1132asp (accessed [today's date]).

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