Is BRIP1 p.Pro210Ser (c.628C>T) pathogenic?

BRIP1 p.Pro210Ser (c.628C>T) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.0707); Ultra-rare (popmax 0.0401%, afr); Associated with BRIP1-related disorder.

What condition is associated with BRIP1 p.Pro210Ser (c.628C>T)?

BRIP1 p.Pro210Ser (c.628C>T) is associated with BRIP1-related disorder, ovarian cancer, Fanconi anemia complementation group J (ClinVar).

How common is BRIP1 p.Pro210Ser (c.628C>T) in the general population?

BRIP1 p.Pro210Ser (c.628C>T) is ultra-rare (popmax 0.0401%, afr) (gnomAD).

What do computational predictors say about BRIP1 p.Pro210Ser (c.628C>T)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

BRIP1 p.Pro210Ser

c.628C>T · rs150313156 · VCV141761

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BRIP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -4.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.5	GERP -1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 68 kb · p 0.065 · regional, not allelic
Overall
CADD	13.63	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

Grpmax group 0.0401% African / African-American · 30/74,898 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00217% 35/1,611,924 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0401%	2,497
Remaining individualsnot grpmax-eligible	0.0048%	20,821
Admixed American	0.00333%	29,989

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.Pro210Ser
Coding: c.628C>T
MANE Select: NM_032043
dbSNP: rs150313156
Type: single nucleotide variant
Location: chr17:61808757 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 210: the helicase atp-binding domain

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

Disease context

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

Similar variants

BRIP1 p.Pro210Leu Uncertain significance ★★ ⚠ same residue
BRIP1 p.Pro210= Benign/Likely benign ★★ same residue
BRIP1 p.Pro210His Conflicting classifications of pathogenicity ★ ⚠ same residue
BRIP1 p.Pro210fs Pathogenic/Likely pathogenic ★★ same residue
BACH1 p.Met210Leu Uncertain significance ★ ⚠ same residue
BACH1 p.Met210Thr Uncertain significance ★ ⚠ same residue
BRIP1 c.1140+1G>A Likely pathogenic ★★ same condition
BRIP1 c.1141-2A>C 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-pro210ser (accessed [today's date]).

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