Is BAZ2B p.Pro1709Ser (c.5125C>T) pathogenic?

BAZ2B p.Pro1709Ser (c.5125C>T) is classified Uncertain significance in BAZ2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-01). AlphaMissense: ambiguous (0.4706); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with BAZ2B p.Pro1709Ser (c.5125C>T)?

BAZ2B p.Pro1709Ser (c.5125C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BAZ2B p.Pro1709Ser (c.5125C>T) in the general population?

BAZ2B p.Pro1709Ser (c.5125C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about BAZ2B p.Pro1709Ser (c.5125C>T)?

AlphaMissense predicts ambiguous (score 0.4706) — an in-silico prediction, not a clinical call.

BAZ2B p.Pro1709Ser

c.5125C>T · rs781214900 · VCV2228805

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4706 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4706	ambiguous
REVEL	0.305	indeterminate
SaProt	LLR -8.27	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 0.78, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 45 kb · p 0.77 · regional, not allelic
Overall
CADD	25.0	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 0.0022% South Asian · 2/91,072 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00149% 24/1,613,888 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,536
European (non-Finnish)	0.00178%	56,189
Remaining individualsnot grpmax-eligible	0.0016%	62,476

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.Pro1709Ser
Coding: c.5125C>T
MANE Select: NM_013450
dbSNP: rs781214900
Type: single nucleotide variant
Location: chr2:159349019 (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.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.Ser1592Cys Uncertain significance ★★ ⚠ same condition
BAZ2B p.Trp826Arg Uncertain significance ★★ ⚠ same condition
BAZ2B p.Ala913Val Likely benign ★★ same condition
BAZ2B p.Arg1008Lys 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-pro1709ser (accessed [today's date]).

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