Is BRCA1 p.Asp1441Asn (c.4321G>A) pathogenic?

BRCA1 p.Asp1441Asn (c.4321G>A) is classified Likely pathogenic in BRCA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). AlphaMissense: likely benign (0.1009); Very rare (popmax 0.0011%, sas).

How common is BRCA1 p.Asp1441Asn (c.4321G>A) in the general population?

BRCA1 p.Asp1441Asn (c.4321G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BRCA1 p.Asp1441Asn (c.4321G>A)?

AlphaMissense predicts likely benign (score 0.1009) — an in-silico prediction, not a clinical call.

BRCA1 p.Asp1441Asn

c.4321G>A · rs757184166 · VCV2687847

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1009 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1009	likely benign ⚠ discordant with ClinVar
REVEL	0.121	moderately benign-leaning
SaProt	LLR -5.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.72, phastCons 0.58
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	11.64	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

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.84e-05% 1/1,461,864 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRCA1
Protein: p.Asp1441Asn
Coding: c.4321G>A
MANE Select: NM_007294
dbSNP: rs757184166
Type: single nucleotide variant
Location: chr17:43082440 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1441: the 'disordered' region; a UniProt-annotated variant site (in fancs)

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

Similar variants

BRCA1 p.Asp1441= Likely benign ★★ same residue
BRCA1 p.Asp1441Glu Uncertain significance ★ ⚠ same residue
BRCA1 p.Asp1441fs Pathogenic ★ same residue
BRCA1 p.Asp1441delinsGlyPhe Uncertain significance ★ 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

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-asp1441asn (accessed [today's date]).

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