Is BRI3 p.Pro5Ala (c.13C>G) pathogenic?

BRI3 p.Pro5Ala (c.13C>G) is classified Uncertain significance in BRI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely benign (0.1498); Very rare (popmax 0.00317%, afr).

How common is BRI3 p.Pro5Ala (c.13C>G) in the general population?

BRI3 p.Pro5Ala (c.13C>G) is very rare (popmax 0.00317%, afr) (gnomAD).

What do computational predictors say about BRI3 p.Pro5Ala (c.13C>G)?

AlphaMissense predicts likely benign (score 0.1498) — an in-silico prediction, not a clinical call.

BRI3 p.Pro5Ala

c.13C>G · rs1261113270 · VCV2527493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00317%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1498	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -8.22	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 5.3	GERP 6.2, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 9,444 bp · p 0.0045 · regional, not allelic
Overall
CADD	21.4	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 0.00317% African / African-American · 2/63,180 alleles

Filtering AF 0.000525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000197%

Overall 0.000163% 2/1,230,466 alleles · very rare exomes 0/1,081,150 · genomes 2/149,316 · joint denominator

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: BRI3
Protein: p.Pro5Ala
Coding: c.13C>G
MANE Select: NM_015379
dbSNP: rs1261113270
Type: single nucleotide variant
Location: chr7:98281808 (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.His3Arg Uncertain significance ★ ⚠ same type
BRI3 p.His52Asp Uncertain significance ★ ⚠ same type
BRI3 p.His52Tyr 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-pro5ala (accessed [today's date]).

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