Is BAZ2B p.Phe60Leu (c.178T>C) pathogenic?

BAZ2B p.Phe60Leu (c.178T>C) is classified Uncertain significance in BAZ2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: ambiguous (0.5149); Very rare (popmax 0.000594%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BAZ2B p.Phe60Leu (c.178T>C)?

BAZ2B p.Phe60Leu (c.178T>C) is associated with Inborn genetic diseases (ClinVar).

How common is BAZ2B p.Phe60Leu (c.178T>C) in the general population?

BAZ2B p.Phe60Leu (c.178T>C) is very rare (popmax 0.000594%, nfe) (gnomAD).

What do computational predictors say about BAZ2B p.Phe60Leu (c.178T>C)?

AlphaMissense predicts ambiguous (score 0.5149) — an in-silico prediction, not a clinical call.

BAZ2B p.Phe60Leu

c.178T>C · VCV4594495

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5149 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5149	ambiguous
REVEL	0.063	moderately benign-leaning
SaProt	LLR -5.03	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 9.3	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 32 kb · p 0.77 · regional, not allelic
Overall
CADD	25.4	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 0.000594% European (non-Finnish) · 7/1,178,622 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,611,070 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: BAZ2B
Protein: p.Phe60Leu
Coding: c.178T>C
MANE Select: NM_013450
Type: single nucleotide variant
Location: chr2:159453769 (GRCh38)
Gene constraint: LOEUF 0.386 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 55.23 · 265 PDB

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.Phe60Ser Uncertain significance ★ ⚠ same residue
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

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-phe60leu (accessed [today's date]).

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