Is BRIP1 p.Ala980Val (c.2939C>T) pathogenic?

BRIP1 p.Ala980Val (c.2939C>T) is classified Conflicting classifications of pathogenicity in BRIP1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-03-06). AlphaMissense: likely benign (0.0834); Very rare (popmax 0.0011%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with BRIP1 p.Ala980Val (c.2939C>T)?

BRIP1 p.Ala980Val (c.2939C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is BRIP1 p.Ala980Val (c.2939C>T) in the general population?

BRIP1 p.Ala980Val (c.2939C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about BRIP1 p.Ala980Val (c.2939C>T)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

BRIP1 p.Ala980Val

c.2939C>T · rs781622986 · VCV1332313

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 0.24, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 110 kb · p 3.3e-06 · regional, not allelic
Overall
CADD	15.45	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 0.0011% South Asian · 1/90,822 alleles

Overall 6.84e-05% 1/1,461,086 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.Ala980Val
Coding: c.2939C>T
MANE Select: NM_032043
dbSNP: rs781622986
Type: single nucleotide variant
Location: chr17:61684107 (GRCh38)
Gene constraint: LOEUF 0.848 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 64.19 · 6 PDB
Residue 980: the 'interaction with brca1' region

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.Ala980Pro Uncertain significance ★★ ⚠ same residue
BRIP1 p.Ala980= Benign/Likely benign ★★ same residue
BRIP1 p.Ala980fs Uncertain significance ★ same residue
BRIP1 p.Ala980Glu 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-ala980val (accessed [today's date]).

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