Is BRCA1 p.Thr1677= (c.5031T>A) pathogenic?

BRCA1 p.Thr1677= (c.5031T>A) is classified Likely benign in BRCA1 (ClinVar, Expert panel, 4 submitters; last evaluated 2017-06-29). Absent from gnomAD v4.1; Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Thr1677= (c.5031T>A)?

BRCA1 p.Thr1677= (c.5031T>A) is associated with breast-ovarian cancer, familial, susceptibility to, 1, hereditary breast ovarian cancer syndrome, hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Thr1677= (c.5031T>A) in the general population?

BRCA1 p.Thr1677= (c.5031T>A) 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.

BRCA1 p.Thr1677=

c.5031T>A · rs765241963 · VCV427338

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP -0.7, phastCons 0.79
Overall
CADD	2.791	PHRED · no single calibrated threshold — expert panels disagree

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.Thr1677=
Coding: c.5031T>A
MANE Select: NM_007294
dbSNP: rs765241963
Type: single nucleotide variant
Location: chr17:43067651 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1677: the brct 1 domain; a UniProt-annotated variant site (in fancs); a β-strand

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

Disease context

breast-ovarian cancer, familial, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary breast ovarian cancer syndrome hereditary neoplastic syndrome

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Thr1677Ile Uncertain significance ★★ ⚠ same residue
BRCA1 p.Thr1677Ala Uncertain significance ★ ⚠ same residue
BRCA1 p.Thr1677Asn Likely benign ★ same residue
BRCA1 p.Thr1677Ser Likely benign ★ same residue
BRCA1 p.Thr1677fs Pathogenic ★★★ same residue
BRCA1 p.Thr1677_Leu1679del Uncertain significance ★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>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-thr1677 (accessed [today's date]).

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