Is BRCA1 p.Asp67Val (c.200A>T) pathogenic?

BRCA1 p.Asp67Val (c.200A>T) is classified Uncertain significance in BRCA1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-05). AlphaMissense: likely benign (0.2364); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Asp67Val (c.200A>T)?

BRCA1 p.Asp67Val (c.200A>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Asp67Val (c.200A>T) in the general population?

BRCA1 p.Asp67Val (c.200A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Asp67Val (c.200A>T)?

AlphaMissense predicts likely benign (score 0.2364) — an in-silico prediction, not a clinical call.

BRCA1 p.Asp67Val

c.200A>T · rs1060502331 · VCV409307

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2364 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,790)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2364	likely benign
REVEL	0.652	pathogenic-leaning
SaProt	LLR -3.24	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.45	GERP -1.4
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	19.69	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

No allele count reported in gnomAD v4.1 (AN 1,596,790). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: BRCA1
Protein: p.Asp67Val
Coding: c.200A>T
MANE Select: NM_007294
dbSNP: rs1060502331
Type: single nucleotide variant
Location: chr17:43106468 (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

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

Also linked: hereditary breast ovarian cancer syndrome

Similar variants

BRCA1 p.Asp67= Benign ★★★ same residue
BRCA1 p.Asp67Tyr Benign ★★★ ⚠ same residue
BRCA1 p.Asp67Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp67Gly Uncertain significance ★ ⚠ same residue
BRCA1 p.Asp67Glu 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-asp67val (accessed [today's date]).

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