Is BBX p.Pro810Ala (c.2428C>G) pathogenic?

BBX p.Pro810Ala (c.2428C>G) is classified Uncertain significance in BBX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.0584); Very rare (popmax 0.00223%, eas).

How common is BBX p.Pro810Ala (c.2428C>G) in the general population?

BBX p.Pro810Ala (c.2428C>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BBX p.Pro810Ala (c.2428C>G)?

AlphaMissense predicts likely benign (score 0.0584) — an in-silico prediction, not a clinical call.

BBX p.Pro810Ala

c.2428C>G · VCV4199167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0584	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 25 kb · p 0.8 · regional, not allelic
Overall
CADD	21.5	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 0.00223% East Asian · 1/44,876 alleles

Overall 0.000124% 2/1,614,054 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
Admixed American	0.00167%	60,024

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.Pro810Ala
Coding: c.2428C>G
MANE Select: NM_001142568
Type: single nucleotide variant
Location: chr3:107798597 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.79
Residue 810: 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-pro810ala (accessed [today's date]).

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