Is BRI3 p.His52Asp (c.154C>G) pathogenic?

BRI3 p.His52Asp (c.154C>G) is classified Uncertain significance in BRI3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely benign (0.3018); Ultra-rare (popmax 0.0165%, mid).

How common is BRI3 p.His52Asp (c.154C>G) in the general population?

BRI3 p.His52Asp (c.154C>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BRI3 p.His52Asp (c.154C>G)?

AlphaMissense predicts likely benign (score 0.3018) — an in-silico prediction, not a clinical call.

BRI3 p.His52Asp

c.154C>G · rs979069467 · VCV2280145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3018 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3018	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.64	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 1.5	GERP 5.7, phastCons 0.011
Regional constraint	o/e 0.78	unconstrained · MANE · 9,444 bp · p 0.0045 · regional, not allelic
Overall
CADD	19.44	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,640 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
European (non-Finnish)	0.000339%	294,965

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.His52Asp
Coding: c.154C>G
MANE Select: NM_015379
dbSNP: rs979069467
Type: single nucleotide variant
Location: chr7:98282362 (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.His52Tyr Uncertain significance ★ ⚠ same residue
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.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-his52asp (accessed [today's date]).

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