Is BRINP2 p.Pro482Leu (c.1445C>T) pathogenic?

BRINP2 p.Pro482Leu (c.1445C>T) is classified Uncertain significance in BRINP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.0695); Very rare (popmax 0.00934%, afr).

How common is BRINP2 p.Pro482Leu (c.1445C>T) in the general population?

BRINP2 p.Pro482Leu (c.1445C>T) is very rare (popmax 0.00934%, afr) (gnomAD).

What do computational predictors say about BRINP2 p.Pro482Leu (c.1445C>T)?

AlphaMissense predicts likely benign (score 0.0695) — an in-silico prediction, not a clinical call.

BRINP2 p.Pro482Leu

c.1445C>T · VCV3993077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0695 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00934%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0695	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -8.03	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 2.3	GERP 2.5, phastCons 0.2
Regional constraint	o/e 0.91	unconstrained · MANE · 51 kb · p 0.018 · regional, not allelic
Overall
CADD	19.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00934% African / African-American · 7/74,940 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00211% 34/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00934%	10,706
Admixed American	0.00333%	30,003
East Asian	0.00223%	44,886
European (non-Finnish)	0.00195%	51,304
Finnishnot grpmax-eligible	0.00156%	64,020

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: BRINP2
Protein: p.Pro482Leu
Coding: c.1445C>T
MANE Select: NM_021165
Type: single nucleotide variant
Location: chr1:177280621 (GRCh38)
Gene constraint: LOEUF 0.411 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.72

Full BRINP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRINP2 p.Tyr279= Benign ★★ same type
BRINP2 p.Ala342Thr Uncertain significance ★ ⚠ same type
BRINP2 p.Ala363Gly Uncertain significance ★ ⚠ same type
BRINP2 p.Ala465Thr Uncertain significance ★ ⚠ same type
BRINP2 p.Ala465Val Uncertain significance ★ ⚠ same type
BRINP2 p.Ala467Thr Uncertain significance ★ ⚠ same type
BRINP2 p.Ala50Thr Uncertain significance ★ ⚠ same type
BRINP2 p.Ala50Val Uncertain significance ★ ⚠ same type

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/brinp2-p-pro482leu (accessed [today's date]).

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