Is BBX p.Glu795Gln (c.2383G>C) pathogenic?

BBX p.Glu795Gln (c.2383G>C) is classified Uncertain significance in BBX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely benign (0.2105); Very rare (popmax 8.48e-05%, nfe).

How common is BBX p.Glu795Gln (c.2383G>C) in the general population?

BBX p.Glu795Gln (c.2383G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about BBX p.Glu795Gln (c.2383G>C)?

AlphaMissense predicts likely benign (score 0.2105) — an in-silico prediction, not a clinical call.

BBX p.Glu795Gln

c.2383G>C · VCV3822358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2105 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2105	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -6.76	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 10	GERP 2.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 25 kb · p 0.8 · regional, not allelic
Overall
CADD	24.3	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 8.48e-05% European (non-Finnish) · 1/1,179,938 alleles

Overall 0.000124% 2/1,613,840 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)grpmax	8.48e-05%	1,179,938

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu795Gln
Coding: c.2383G>C
MANE Select: NM_001142568
Type: single nucleotide variant
Location: chr3:107798552 (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-glu795gln (accessed [today's date]).

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