Is BRCA1 p.Cys27Ser (c.80G>C) pathogenic?

BRCA1 p.Cys27Ser (c.80G>C) is classified Conflicting classifications of pathogenicity in BRCA1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-09-18). AlphaMissense: likely pathogenic (0.9941); Absent from gnomAD v4.1; Associated with hereditary breast ovarian cancer syndrome.

What condition is associated with BRCA1 p.Cys27Ser (c.80G>C)?

BRCA1 p.Cys27Ser (c.80G>C) is associated with hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Cys27Ser (c.80G>C) in the general population?

BRCA1 p.Cys27Ser (c.80G>C) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast and/or ovarian cancer syndrome inherited?

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

What do computational predictors say about BRCA1 p.Cys27Ser (c.80G>C)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

BRCA1 p.Cys27Ser

c.80G>C · rs1064793052 · VCV418064

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast ovarian cancer syndrome

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic · top 1% in BRCA1
REVEL	0.95	strongly pathogenic-leaning
SaProt	LLR -15.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.56	donor loss at this position · raw score · deltas
Pangolin	Δ0.43	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRCA1
Protein: p.Cys27Ser
Coding: c.80G>C
MANE Select: NM_007294
dbSNP: rs1064793052
Type: single nucleotide variant
Location: chr17:43124017 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 27: a β-strand

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

Disease context

hereditary breast ovarian cancer syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary breast and/or ovarian cancer syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Cys27Phe Likely pathogenic ★★ same residue
BRCA1 p.Cys27Tyr Likely pathogenic ★★ same residue
BRCA1 p.Cys27= Likely benign ★★ same residue
BRCA1 p.Cys27_Leu28insIleCys Uncertain significance ★★ same residue
BRCA1 p.Cys27Trp Likely pathogenic ★★ same residue
BRCA1 p.Cys27Arg Likely pathogenic ★ same residue
BRCA1 p.Cys27Gly Likely pathogenic ★ same residue
BRCA1 c.134+3A>T Likely 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-cys27ser (accessed [today's date]).

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