Is BRINP2 p.Ser367Arg (c.1101C>A) pathogenic?

BRINP2 p.Ser367Arg (c.1101C>A) is classified Uncertain significance in BRINP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.2372); Ultra-rare (popmax 0.02%, afr).

How common is BRINP2 p.Ser367Arg (c.1101C>A) in the general population?

BRINP2 p.Ser367Arg (c.1101C>A) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about BRINP2 p.Ser367Arg (c.1101C>A)?

AlphaMissense predicts likely benign (score 0.2372) — an in-silico prediction, not a clinical call.

BRINP2 p.Ser367Arg

c.1101C>A · VCV3825633

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2372 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2372	likely benign
REVEL	0.07	moderately benign-leaning
SaProt	LLR -6.37	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 1.1	GERP 1.4, phastCons 0.56
Regional constraint	o/e 0.91	unconstrained · MANE · 51 kb · p 0.018 · regional, not allelic
Overall
CADD	17.19	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 0.02% African / African-American · 15/74,944 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.000991% 16/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,996
European (non-Finnish)	8.47e-05%	1,180,054

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.Ser367Arg
Coding: c.1101C>A
MANE Select: NM_021165
Type: single nucleotide variant
Location: chr1:177278651 (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-ser367arg (accessed [today's date]).

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