Is BRCA1 p.Lys1702Asn (c.5106A>T) pathogenic?

BRCA1 p.Lys1702Asn (c.5106A>T) is classified Likely pathogenic in BRCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2026-04-08). AlphaMissense: likely pathogenic (0.9755); Absent from gnomAD v4.1; Associated with Inherited breast cancer and ovarian cancer.

What condition is associated with BRCA1 p.Lys1702Asn (c.5106A>T)?

BRCA1 p.Lys1702Asn (c.5106A>T) is associated with Inherited breast cancer and ovarian cancer (ClinVar).

How common is BRCA1 p.Lys1702Asn (c.5106A>T) in the general population?

BRCA1 p.Lys1702Asn (c.5106A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Lys1702Asn (c.5106A>T)?

AlphaMissense predicts likely pathogenic (score 0.9755) — an in-silico prediction, not a clinical call.

BRCA1 p.Lys1702Asn

c.5106A>T · rs1060504574 · VCV868654

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9755 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inherited breast cancer and ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.9755	likely pathogenic ✓ concordant with ClinVar · top 1% in BRCA1
REVEL	0.672	pathogenic-leaning
SaProt	LLR -10.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP 0.54, phastCons 0.34
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	21.2	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.Lys1702Asn
Coding: c.5106A>T
MANE Select: NM_007294
dbSNP: rs1060504574
Type: single nucleotide variant
Location: chr17:43063920 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1702: the brct 1 domain; a UniProt-annotated variant site (in fancs); an α-helix

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

Disease context

Inherited breast cancer and ovarian cancer

Similar variants

BRCA1 p.Lys1702Gln Likely pathogenic ★ same residue
BRCA1 p.Lys1702= Conflicting classifications of pathogenicity ★ same residue
BRCA1 p.Lys1702Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Lys1702Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Lys1702fs Pathogenic ★★★ same residue
BRCA1 c.135-1G>A Pathogenic/Likely pathogenic ★★ same condition
BRCA1 c.212+2T>C Pathogenic/Likely pathogenic ★★ same condition
BRCA1 c.441+1G>A Pathogenic/Likely 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-lys1702asn (accessed [today's date]).

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