Is BBX p.Met929Ile (c.2787G>A) pathogenic?

BBX p.Met929Ile (c.2787G>A) is classified Uncertain significance in BBX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: ambiguous (0.5047); Rare (popmax 0.101%, afr).

How common is BBX p.Met929Ile (c.2787G>A) in the general population?

BBX p.Met929Ile (c.2787G>A) is rare (popmax 0.101%, afr) (gnomAD).

What do computational predictors say about BBX p.Met929Ile (c.2787G>A)?

AlphaMissense predicts ambiguous (score 0.5047) — an in-silico prediction, not a clinical call.

BBX p.Met929Ile

c.2787G>A · rs148463172 · VCV2376405

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5047 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.101%, afr)

Computational evidence

Protein change
AlphaMissense	0.5047	ambiguous
REVEL	0.487	indeterminate
SaProt	LLR -5.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 6,762 bp · p 0.014 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.101% African / African-American · 76/74,924 alleles

Filtering AF 0.083% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0763%

Overall 0.00539% 87/1,613,982 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.101%	986
Middle Eastern	0.0493%	2,028
Remaining individualsnot grpmax-eligible	0.0096%	10,413
South Asian	0.0022%	45,542

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: BBX
Protein: p.Met929Ile
Coding: c.2787G>A
MANE Select: NM_001142568
dbSNP: rs148463172
Type: single nucleotide variant
Location: chr3:107805418 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.79
Residue 929: the 'disordered' region

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

Similar variants

BBX p.Ala442Thr Benign ★★ same type
BBX p.Ala60= Likely benign ★★ same type
BBX p.Ala892= Benign ★★ same type
BBX p.Ala139Thr Uncertain significance ★ ⚠ same type
BBX p.Ala143Gly Uncertain significance ★ ⚠ same type
BBX p.Ala269Pro Uncertain significance ★ ⚠ same type
BBX p.Ala354Thr Uncertain significance ★ ⚠ same type
BBX p.Ala375Thr 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/bbx-p-met929ile (accessed [today's date]).

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