Is BAZ2B p.Val2129Phe (c.6385G>T) pathogenic?

BAZ2B p.Val2129Phe (c.6385G>T) is classified Uncertain significance in BAZ2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely pathogenic (0.818); Ultra-rare (popmax 0.018%, afr); Associated with Inborn genetic diseases.

What condition is associated with BAZ2B p.Val2129Phe (c.6385G>T)?

BAZ2B p.Val2129Phe (c.6385G>T) is associated with Inborn genetic diseases (ClinVar).

How common is BAZ2B p.Val2129Phe (c.6385G>T) in the general population?

BAZ2B p.Val2129Phe (c.6385G>T) is ultra-rare (popmax 0.018%, afr) (gnomAD).

What do computational predictors say about BAZ2B p.Val2129Phe (c.6385G>T)?

AlphaMissense predicts likely pathogenic (score 0.818) — an in-silico prediction, not a clinical call.

BAZ2B p.Val2129Phe

c.6385G>T · VCV4197861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.818	likely pathogenic
REVEL	0.374	indeterminate
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 12 kb · p 0.14 · regional, not allelic
Overall
CADD	24.1	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 0.018% African / African-American · 13/72,084 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00842%

Overall 0.000825% 13/1,575,912 alleles · ultra-rare exomes 3/1,423,784 · genomes 10/152,128 · joint denominator

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.Val2129Phe
Coding: c.6385G>T
MANE Select: NM_013450
Type: single nucleotide variant
Location: chr2:159320387 (GRCh38)
Gene constraint: LOEUF 0.386 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 55.23 · 265 PDB
Residue 2129: the bromo domain; an α-helix

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-val2129phe (accessed [today's date]).

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