Is BRI3 p.His3Arg (c.8A>G) pathogenic?

BRI3 p.His3Arg (c.8A>G) is classified Uncertain significance in BRI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-12). AlphaMissense: likely benign (0.242); Absent from gnomAD v4.1.

How common is BRI3 p.His3Arg (c.8A>G) in the general population?

BRI3 p.His3Arg (c.8A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BRI3 p.His3Arg (c.8A>G)?

AlphaMissense predicts likely benign (score 0.242) — an in-silico prediction, not a clinical call.

BRI3 p.His3Arg

c.8A>G · VCV3993058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.242 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.242	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.97	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 7.1	GERP 6.2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 9,444 bp · p 0.0045 · regional, not allelic
Overall
CADD	20.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BRI3
Protein: p.His3Arg
Coding: c.8A>G
MANE Select: NM_015379
Type: single nucleotide variant
Location: chr7:98281803 (GRCh38)
Gene constraint: LOEUF 1.326 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 65.20

Full BRI3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BRI3 p.His60= Benign ★★ same type
BAIAP2L1 p.Ile510Thr Uncertain significance ★ ⚠ same type
BAIAP2L1 p.Lys183Arg Uncertain significance ★ ⚠ same type
BRI3 p.Glu9Gly Uncertain significance ★ ⚠ same type
BRI3 p.Gly26Ser Uncertain significance ★ ⚠ same type
BRI3 p.His52Asp Uncertain significance ★ ⚠ same type
BRI3 p.His52Tyr Uncertain significance ★ ⚠ same type
BRI3 p.Ile49Met 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/bri3-p-his3arg (accessed [today's date]).

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