Is BRCA1 p.Val199= (c.597G>A) pathogenic?

BRCA1 p.Val199= (c.597G>A) is classified Uncertain significance in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-31). Absent from gnomAD v4.1.

How common is BRCA1 p.Val199= (c.597G>A) in the general population?

BRCA1 p.Val199= (c.597G>A) is absent from gnomAD v4.1 (gnomAD).

BRCA1 p.Val199=

c.597G>A · VCV4533113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Pangolin	Δ0.21	gain · loss 0.19 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 0.29	GERP -0.32, phastCons 0.001
Overall
CADD	13.08	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.Val199=
Coding: c.597G>A
MANE Select: NM_007294
Type: single nucleotide variant
Location: chr17:43095919 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB

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

Similar variants

BRCA1 p.Val199Ala Uncertain significance ★ ⚠ same residue
BRCA1 p.Val199Met Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same type
BRCA1 c.135-1G>T Pathogenic ★★★ same type
BRCA1 c.212+1G>A Pathogenic ★★★ same type
BRCA1 c.212+1G>T Pathogenic ★★★ same type
BRCA1 c.212+3A>G Pathogenic ★★★ same type
BRCA1 c.213-12A>G Pathogenic ★★★ same type

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-val199 (accessed [today's date]).

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