Is BRCA1 p.Asp1692Asn (c.5074G>A) pathogenic?

BRCA1 p.Asp1692Asn (c.5074G>A) is classified Pathogenic in BRCA1 (ClinVar, Expert panel, 17 submitters; last evaluated 2026-09-21). AlphaMissense: likely benign (0.2943); Absent from gnomAD v4.1; Associated with BRCA1-related cancer predisposition.

What condition is associated with BRCA1 p.Asp1692Asn (c.5074G>A)?

BRCA1 p.Asp1692Asn (c.5074G>A) is associated with BRCA1-related cancer predisposition, urinary bladder cancer, hereditary breast ovarian cancer syndrome (ClinVar).

How common is BRCA1 p.Asp1692Asn (c.5074G>A) in the general population?

BRCA1 p.Asp1692Asn (c.5074G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Asp1692Asn (c.5074G>A)?

AlphaMissense predicts likely benign (score 0.2943) — an in-silico prediction, not a clinical call.

BRCA1 p.Asp1692Asn

c.5074G>A · rs80187739 · VCV37632

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 17 submitters

AlphaMissense

likely benign

0.2943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BRCA1-related cancer predisposition

Computational evidence

Protein change
AlphaMissense	0.2943	likely benign ⚠ discordant with ClinVar
REVEL	0.463	indeterminate
SaProt	LLR -4.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.73	donor loss at this position · raw score · deltas
Pangolin	Δ0.70	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	32.0	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.Asp1692Asn
Coding: c.5074G>A
MANE Select: NM_007294
dbSNP: rs80187739
Type: single nucleotide variant
Location: chr17:43067608 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1692: the brct 1 domain; a UniProt-annotated variant site (in fancs); a UniProt-annotated variant site (in ovarian cancer; uncertain significance)

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

Disease context

Also linked: urinary bladder cancer hereditary breast ovarian cancer syndrome breast-ovarian cancer, familial, susceptibility to, 1 hereditary neoplastic syndrome

Similar variants

BRCA1 p.Asp1692His Pathogenic ★★★ same residue
BRCA1 p.Asp1692Val Likely pathogenic ★★★ same residue
BRCA1 p.Asp1692Tyr Pathogenic ★ same residue
BRCA1 p.Asp1692Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp1692Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Asp1692fs Pathogenic ★★★ same residue
BRCA1 p.Asp1692_Trp1718delinsGly Pathogenic ★ same residue
BRCA1 c.134+3A>T 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-asp1692asn (accessed [today's date]).

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