Is BRCA1 p.Ala1830Ser (c.5488G>T) pathogenic?

BRCA1 p.Ala1830Ser (c.5488G>T) is classified Likely pathogenic in BRCA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-01-01). AlphaMissense: likely benign (0.1234); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with BRCA1 p.Ala1830Ser (c.5488G>T)?

BRCA1 p.Ala1830Ser (c.5488G>T) is associated with ovarian cancer (ClinVar).

How common is BRCA1 p.Ala1830Ser (c.5488G>T) in the general population?

BRCA1 p.Ala1830Ser (c.5488G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRCA1 p.Ala1830Ser (c.5488G>T)?

AlphaMissense predicts likely benign (score 0.1234) — an in-silico prediction, not a clinical call.

BRCA1 p.Ala1830Ser

c.5488G>T · rs80357393 · VCV864931

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1234 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.1234	likely benign ⚠ discordant with ClinVar
REVEL	0.497	indeterminate
SaProt	LLR -8.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.6, phastCons 0.34
Regional constraint	o/e 0.91	unconstrained · MANE · 78 kb · p 4.8e-05 · regional, not allelic
Overall
CADD	19.82	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.Ala1830Ser
Coding: c.5488G>T
MANE Select: NM_007294
dbSNP: rs80357393
Type: single nucleotide variant
Location: chr17:43045782 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 41.99 · 33 PDB
Residue 1830: a UniProt-annotated variant site (in fancs); the brct 2 domain; a β-strand

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

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRCA1 p.Ala1830Glu Uncertain significance ★★ ⚠ same residue
BRCA1 p.Ala1830Gly Uncertain significance ★ same residue
BRCA1 p.Ala1830Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
BRCA1 p.Ala1830Val Uncertain significance ★ ⚠ same residue
BRCA1 p.Arg1203Ter Pathogenic ★★★ same condition
BRCA1 p.Arg1699Trp Pathogenic ★★★ same condition
BRCA1 p.Gln1273Ter Pathogenic ★★★ same condition
BRCA1 p.Gln541Ter 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-ala1830ser (accessed [today's date]).

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