Is BRCA2 p.Cys1885= (c.5655C>T) pathogenic?

BRCA2 p.Cys1885= (c.5655C>T) is classified Likely benign in BRCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-12-09). Very rare (popmax 0.00773%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA2 p.Cys1885= (c.5655C>T)?

BRCA2 p.Cys1885= (c.5655C>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA2 p.Cys1885= (c.5655C>T) in the general population?

BRCA2 p.Cys1885= (c.5655C>T) is very rare (popmax 0.00773%, sas) (gnomAD).

BRCA2 p.Cys1885=

c.5655C>T · rs80358789 · VCV796332

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00773%, sas)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.061	GERP 1.2
Overall
CADD	1.108	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00773% South Asian · 7/90,584 alleles

Filtering AF 0.00361% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00256%

Overall 0.000496% 8/1,612,522 alleles · very rare exomes 6/1,460,460 · genomes 2/152,062 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00773%	12,941
European (non-Finnish)	8.48e-05%	1,179,601

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.Cys1885=
Coding: c.5655C>T
MANE Select: NM_000059
dbSNP: rs80358789
Type: single nucleotide variant
Location: chr13:32340010 (GRCh38)
Gene constraint: LOEUF 0.803 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Residue 1885: the 'interaction with rad51' 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.Cys1885Ter Pathogenic ★★★ same residue
BRCA2 p.Cys1885Phe Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Cys1885Trp Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Cys1885Tyr Conflicting classifications of pathogenicity ★ same residue
BRCA2 p.Cys1885fs Pathogenic ★★★ same residue
BRCA2 p.Cys1885Arg Uncertain significance 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-cys1885 (accessed [today's date]).

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