Is BBX p.Asn910His (c.2728A>C) pathogenic?

BBX p.Asn910His (c.2728A>C) is classified Uncertain significance in BBX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely pathogenic (0.7887); Very rare (popmax 0.00133%, afr).

How common is BBX p.Asn910His (c.2728A>C) in the general population?

BBX p.Asn910His (c.2728A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about BBX p.Asn910His (c.2728A>C)?

AlphaMissense predicts likely pathogenic (score 0.7887) — an in-silico prediction, not a clinical call.

BBX p.Asn910His

c.2728A>C · VCV3990826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7887	likely pathogenic
REVEL	0.518	indeterminate
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 6,762 bp · p 0.014 · regional, not allelic
Overall
CADD	26.3	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 0.00133% African / African-American · 1/74,914 alleles

Overall 0.000657% 1/152,168 alleles · very rare

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.Asn910His
Coding: c.2728A>C
MANE Select: NM_001142568
Type: single nucleotide variant
Location: chr3:107801271 (GRCh38)
Gene constraint: LOEUF 0.359 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 50.79

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-asn910his (accessed [today's date]).

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