Is BRCA2 p.Asn1833Ser (c.5498A>G) pathogenic?

BRCA2 p.Asn1833Ser (c.5498A>G) is classified Conflicting classifications of pathogenicity in BRCA2 (ClinVar, Conflicting submitters, 13 submitters; last evaluated 2025-11-21). AlphaMissense: likely benign (0.078); Ultra-rare (popmax 0.0294%, afr); Associated with BRCA2-related cancer predisposition.

What condition is associated with BRCA2 p.Asn1833Ser (c.5498A>G)?

BRCA2 p.Asn1833Ser (c.5498A>G) is associated with BRCA2-related cancer predisposition, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 2 (ClinVar).

How common is BRCA2 p.Asn1833Ser (c.5498A>G) in the general population?

BRCA2 p.Asn1833Ser (c.5498A>G) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about BRCA2 p.Asn1833Ser (c.5498A>G)?

AlphaMissense predicts likely benign (score 0.078) — an in-silico prediction, not a clinical call.

BRCA2 p.Asn1833Ser

c.5498A>G · rs587782601 · VCV142634

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 13 submitters

AlphaMissense

likely benign

0.078 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

BRCA2-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.078	likely benign
REVEL	0.136	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 4.5	GERP 1.3, phastCons 0.17
Regional constraint	o/e 1.03	unconstrained · MANE · 47 kb · p 0.059 · regional, not allelic
Overall
CADD	11.68	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 0.0294% African / African-American · 22/74,894 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00136% 22/1,613,278 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: BRCA2
Protein: p.Asn1833Ser
Coding: c.5498A>G
MANE Select: NM_000059
dbSNP: rs587782601
Type: single nucleotide variant
Location: chr13:32339853 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1833: the 'interaction with rad51' region

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

Disease context

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

Similar variants

BRCA2 p.Asn1833Lys Uncertain significance ★★ ⚠ same residue
BRCA2 p.Asn1833= Likely benign ★★ same residue
BRCA2 p.Asn1833Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA2 p.Asn1833fs Pathogenic ★★★ same residue
BRCA2 p.Asn1833Ter Pathogenic ★★★ same residue
BRCA2 p.Asn1833_Ser1834insTer Pathogenic ★ same residue
BRCA2 c.316+1G>T Pathogenic ★★★ same condition
BRCA2 c.316+2T>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-asn1833ser (accessed [today's date]).

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