Is BRCA1 p.Ala1823Thr (c.5467G>A) pathogenic?

BRCA1 p.Ala1823Thr (c.5467G>A) is classified Pathogenic/Likely pathogenic in BRCA1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-04-24). AlphaMissense: likely benign (0.0828); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with BRCA1 p.Ala1823Thr (c.5467G>A)?

BRCA1 p.Ala1823Thr (c.5467G>A) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, breast-ovarian cancer, familial, susceptibility to, 1 (ClinVar).

How common is BRCA1 p.Ala1823Thr (c.5467G>A) in the general population?

BRCA1 p.Ala1823Thr (c.5467G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Ala1823Thr (c.5467G>A)?

AlphaMissense predicts likely benign (score 0.0828) — an in-silico prediction, not a clinical call.

BRCA1 p.Ala1823Thr

c.5467G>A · rs80357212 · VCV55588

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0828	likely benign ⚠ discordant with ClinVar
REVEL	0.485	indeterminate
SaProt	LLR -3.49	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.72	donor loss at this position · raw score · deltas
Pangolin	Δ0.65	loss · gain 0.06 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	24.6	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.Ala1823Thr
Coding: c.5467G>A
MANE Select: NM_007294
dbSNP: rs80357212
Type: single nucleotide variant
Location: chr17:43047643 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1823: a UniProt-annotated variant site (in fancs); the brct 2 domain

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

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

Similar variants

BRCA1 p.Ala1823Ser Pathogenic ★★ ⚠ same residue
BRCA1 p.Ala1823= Likely benign ★★ same residue
BRCA1 p.Ala1823Pro Likely pathogenic ★ ⚠ same residue
BRCA1 p.Ala1823Glu Uncertain significance ★ ⚠ same residue
BRCA1 p.Ala1823fs Pathogenic ★★★ same residue
BRCA1 c.134+3A>T Likely pathogenic ★★★ same condition
BRCA1 c.135-1G>T Pathogenic ★★★ same condition
BRCA1 c.212+1G>A 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-ala1823thr (accessed [today's date]).

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