Is BRCA1 p.Val1713Leu (c.5137G>T) pathogenic?

BRCA1 p.Val1713Leu (c.5137G>T) is classified Likely pathogenic in BRCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-10-28). AlphaMissense: likely pathogenic (0.6085); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Val1713Leu (c.5137G>T)?

BRCA1 p.Val1713Leu (c.5137G>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRCA1 p.Val1713Leu (c.5137G>T) in the general population?

BRCA1 p.Val1713Leu (c.5137G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Val1713Leu (c.5137G>T)?

AlphaMissense predicts likely pathogenic (score 0.6085) — an in-silico prediction, not a clinical call.

BRCA1 p.Val1713Leu

c.5137G>T · rs1064793309 · VCV868700

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6085 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.6085	likely pathogenic ✓ concordant with ClinVar · top 7% in BRCA1
REVEL	0.564	indeterminate
SaProt	LLR -8.05	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.52	donor gain, 2 bp away · raw score · deltas
Pangolin	Δ0.40	gain · loss 0.04 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 1.1	GERP -3.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	23.2	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.Val1713Leu
Coding: c.5137G>T
MANE Select: NM_007294
dbSNP: rs1064793309
Type: single nucleotide variant
Location: chr17:43063889 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1713: the brct 1 domain; a UniProt-annotated variant site (in fancs); a UniProt-annotated variant site (sequence variant); a β-strand

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

Similar variants

BRCA1 p.Val1713Ala Likely pathogenic ★★★ same residue
BRCA1 p.Val1713Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Val1713= Likely benign ★ same residue
BRCA1 p.Val1713fs Pathogenic ★★ same residue
BRCA1 p.Val1713Gly Pathogenic ★ same residue
BRCA1 p.Val1713Glu 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-val1713leu (accessed [today's date]).

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