Is BAZ2B p.Leu766Phe (c.2296C>T) pathogenic?

BAZ2B p.Leu766Phe (c.2296C>T) is classified Uncertain significance in BAZ2B (ClinVar, Single submitter, 2 submitters; last evaluated 2025-07-13). AlphaMissense: ambiguous (0.4022); Ultra-rare (popmax 0.0347%, afr); Associated with Inborn genetic diseases.

What condition is associated with BAZ2B p.Leu766Phe (c.2296C>T)?

BAZ2B p.Leu766Phe (c.2296C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BAZ2B p.Leu766Phe (c.2296C>T) in the general population?

BAZ2B p.Leu766Phe (c.2296C>T) is ultra-rare (popmax 0.0347%, afr) (gnomAD).

What do computational predictors say about BAZ2B p.Leu766Phe (c.2296C>T)?

AlphaMissense predicts ambiguous (score 0.4022) — an in-silico prediction, not a clinical call.

BAZ2B p.Leu766Phe

c.2296C>T · rs769049985 · VCV3053947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4022 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0347%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4022	ambiguous
REVEL	0.654	pathogenic-leaning
SaProt	LLR -4.96	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 0.85, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 38 kb · p 1 · regional, not allelic
Overall
CADD	23.8	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 0.0347% African / African-American · 26/74,844 alleles

Filtering AF 0.0243% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0208%

Overall 0.00174% 28/1,613,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0347%	2,879
East Asian	0.00223%	44,804
Admixed American	0.00167%	59,954

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: BAZ2B
Protein: p.Leu766Phe
Coding: c.2296C>T
MANE Select: NM_013450
dbSNP: rs769049985
Type: single nucleotide variant
Location: chr2:159428379 (GRCh38)
Gene constraint: LOEUF 0.386 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 55.23 · 265 PDB
Residue 766: the mbd domain; a β-strand

Full BAZ2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BAZ2B p.Arg1290Gln Uncertain significance ★★ ⚠ same condition
BAZ2B p.Ile502Val Uncertain significance ★★ ⚠ same condition
BAZ2B p.Leu587Ser Uncertain significance ★★ ⚠ same condition
BAZ2B p.Met1013Ile Uncertain significance ★★ ⚠ same condition
BAZ2B p.Pro1709Ser Uncertain significance ★★ ⚠ same condition
BAZ2B p.Ser1592Cys Uncertain significance ★★ ⚠ same condition
BAZ2B p.Trp826Arg Uncertain significance ★★ ⚠ same condition
BAZ2B p.Ala913Val Likely benign ★★ same condition

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/baz2b-p-leu766phe (accessed [today's date]).

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