Is BRIP1 p.Ser542= (c.1626C>T) pathogenic?

BRIP1 p.Ser542= (c.1626C>T) is classified Benign/Likely benign in BRIP1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-01). Rare (popmax 0.22%, sas); Associated with familial ovarian cancer.

What condition is associated with BRIP1 p.Ser542= (c.1626C>T)?

BRIP1 p.Ser542= (c.1626C>T) is associated with familial ovarian cancer, Fanconi anemia complementation group J, hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Ser542= (c.1626C>T) in the general population?

BRIP1 p.Ser542= (c.1626C>T) is rare (popmax 0.22%, sas) (gnomAD).

BRIP1 p.Ser542=

c.1626C>T · rs373709958 · VCV183873

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.22%, sas)

Conditions

familial ovarian cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP 1.3, phastCons 1
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.22% South Asian · 200/90,912 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.185%

Overall 0.0151% 244/1,611,820 alleles · rare exomes 226/1,459,600 · genomes 18/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.22%	455
Middle Eastern	0.0173%	5,766
Admixed American	0.015%	6,667
Remaining individualsnot grpmax-eligible	0.00962%	10,399
African / African-American	0.00267%	37,473
European (non-Finnish)	0.00221%	45,328

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.Ser542=
Coding: c.1626C>T
MANE Select: NM_032043
dbSNP: rs373709958
Type: single nucleotide variant
Location: chr17:61784272 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB

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

Disease context

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

Also linked: Fanconi anemia complementation group J hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

BRIP1 p.Ser542Asn Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser542Ile Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ser542del Uncertain significance ★★ same residue
BRIP1 p.Ser542Arg 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

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-ser542 (accessed [today's date]).

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