Is BRIP1 p.Ser53= (c.159C>T) pathogenic?

BRIP1 p.Ser53= (c.159C>T) is classified Likely benign in BRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-04). Very rare (popmax 0.00833%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Ser53= (c.159C>T)?

BRIP1 p.Ser53= (c.159C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Ser53= (c.159C>T) in the general population?

BRIP1 p.Ser53= (c.159C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

BRIP1 p.Ser53=

c.159C>T · rs779686432 · VCV765273

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.1	GERP -1.1, phastCons 1
Overall
CADD	8.267	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,028 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000342% 5/1,461,688 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: BRIP1
Protein: p.Ser53=
Coding: c.159C>T
MANE Select: NM_032043
dbSNP: rs779686432
Type: single nucleotide variant
Location: chr17:61859842 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 53: the helicase atp-binding domain

Full BRIP1 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

Similar variants

BRIP1 p.Ser53Asn Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser53fs Pathogenic ★★ same residue
BRIP1 p.Ser53Ile Uncertain significance ★★ same residue
BRIP1 p.Ser53Thr Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>G Likely pathogenic ★★ same condition
BRIP1 c.1340+1G>A Pathogenic/Likely pathogenic ★★ same condition
BRIP1 c.1341-1G>A 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-ser53 (accessed [today's date]).

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