Is BAZ2B p.Phe591Cys (c.1772T>G) pathogenic?

BAZ2B p.Phe591Cys (c.1772T>G) is classified Likely benign in BAZ2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: ambiguous (0.3716); Very rare (popmax 0.00263%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BAZ2B p.Phe591Cys (c.1772T>G)?

BAZ2B p.Phe591Cys (c.1772T>G) is associated with Inborn genetic diseases (ClinVar).

How common is BAZ2B p.Phe591Cys (c.1772T>G) in the general population?

BAZ2B p.Phe591Cys (c.1772T>G) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about BAZ2B p.Phe591Cys (c.1772T>G)?

AlphaMissense predicts ambiguous (score 0.3716) — an in-silico prediction, not a clinical call.

BAZ2B p.Phe591Cys

c.1772T>G · VCV4594446

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3716	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -6.96	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 38 kb · p 1 · regional, not allelic
Overall
CADD	24.4	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 0.00263% European (non-Finnish) · 31/1,180,022 alleles

Filtering AF 0.00188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00211% 34/1,613,964 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00263%	38,065
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,486
South Asian	0.0011%	91,080

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.Phe591Cys
Coding: c.1772T>G
MANE Select: NM_013450
Type: single nucleotide variant
Location: chr2:159432885 (GRCh38)
Gene constraint: LOEUF 0.386 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 55.23 · 265 PDB
Residue 591: the 'disordered' region

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-phe591cys (accessed [today's date]).

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