Is BRCA1 p.Asp67Tyr (c.199G>T) pathogenic?

BRCA1 p.Asp67Tyr (c.199G>T) is classified Benign in BRCA1 (ClinVar, Expert panel, 24 submitters; last evaluated 2015-08-10). AlphaMissense: likely benign (0.2168); Ultra-rare (popmax 0.0108%, nfe); Associated with breast-ovarian cancer, familial, susceptibility to, 1.

What condition is associated with BRCA1 p.Asp67Tyr (c.199G>T)?

BRCA1 p.Asp67Tyr (c.199G>T) is associated with breast-ovarian cancer, familial, susceptibility to, 1, hereditary breast ovarian cancer syndrome, breast cancer (ClinVar).

How common is BRCA1 p.Asp67Tyr (c.199G>T) in the general population?

BRCA1 p.Asp67Tyr (c.199G>T) is ultra-rare (popmax 0.0108%, nfe) (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.Asp67Tyr (c.199G>T)?

AlphaMissense predicts likely benign (score 0.2168) — an in-silico prediction, not a clinical call.

BRCA1 p.Asp67Tyr

c.199G>T · rs80357102 · VCV54431

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 24 submitters

AlphaMissense

likely benign

0.2168 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0108%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

breast-ovarian cancer, familial, susceptibility to, 1

Computational evidence

Protein change
AlphaMissense	0.2168	likely benign
REVEL	0.658	pathogenic-leaning
SaProt	LLR -4.37	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.025	GERP -3.3
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	18.03	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 0.0108% European (non-Finnish) · 126/1,165,696 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00865%

Overall 0.00827% 132/1,596,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0108%	9,252
Remaining individualsnot grpmax-eligible	0.00485%	20,623
Admixed American	0.00334%	29,930
African / African-American	0.00134%	74,666

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.Asp67Tyr
Coding: c.199G>T
MANE Select: NM_007294
dbSNP: rs80357102
Type: single nucleotide variant
Location: chr17:43106469 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 67: a β-strand; a UniProt-annotated variant site (in bc; benign; functionally neutral in vitro)

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 breast cancer pancreatic cancer, susceptibility to, 4 hereditary neoplastic syndrome hereditary breast carcinoma Fanconi anemia, complementation group S

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

Inheritance: Autosomal dominant
Onset: Adult, Elderly

Similar variants

BRCA1 p.Asp67= Benign ★★★ same residue
BRCA1 p.Asp67Val Uncertain significance ★★ ⚠ same residue
BRCA1 p.Asp67Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp67Glu Uncertain significance ★ ⚠ same residue
BRCA1 p.Asp67Gly Uncertain significance ★ ⚠ same residue
BRCA1 p.Asp67Asn 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-asp67tyr (accessed [today's date]).

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