Is BRIP1 p.Ser1237Tyr (c.3710C>A) pathogenic?

BRIP1 p.Ser1237Tyr (c.3710C>A) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2021-08-31). AlphaMissense: likely benign (0.0851); Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with BRIP1 p.Ser1237Tyr (c.3710C>A)?

BRIP1 p.Ser1237Tyr (c.3710C>A) is associated with hereditary breast carcinoma, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Ser1237Tyr (c.3710C>A) in the general population?

BRIP1 p.Ser1237Tyr (c.3710C>A) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BRIP1 p.Ser1237Tyr (c.3710C>A)?

AlphaMissense predicts likely benign (score 0.0851) — an in-silico prediction, not a clinical call.

BRIP1 p.Ser1237Tyr

c.3710C>A · rs587781819 · VCV506573

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.0851	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -8.84	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.21	donor loss, 17 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.3	GERP 0.84, phastCons 0.85
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	12.83	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: BRIP1
Protein: p.Ser1237Tyr
Coding: c.3710C>A
MANE Select: NM_032043
dbSNP: rs587781819
Type: single nucleotide variant
Location: chr17:61683336 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 1237: a modified residue (phosphoserine)

Full BRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Fanconi anemia complementation group J

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

BRIP1 p.Ser1237Phe Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser1237= Likely benign ★★ same residue
BRIP1 p.Ser1237Thr Uncertain significance ★★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>C Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>G Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>T Likely pathogenic ★★ same condition
BRIP1 c.1340+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/brip1-p-ser1237tyr (accessed [today's date]).

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