Is UNC45B p.Arg434= (c.1302C>T) pathogenic?

UNC45B p.Arg434= (c.1302C>T) is classified Likely benign in UNC45B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-17). Ultra-rare (popmax 0.0172%, amr); Associated with UNC45B-related disorder.

What condition is associated with UNC45B p.Arg434= (c.1302C>T)?

UNC45B p.Arg434= (c.1302C>T) is associated with UNC45B-related disorder (ClinVar).

How common is UNC45B p.Arg434= (c.1302C>T) in the general population?

UNC45B p.Arg434= (c.1302C>T) is ultra-rare (popmax 0.0172%, amr) (gnomAD).

UNC45B p.Arg434=

c.1302C>T · rs113010242 · VCV3036876

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, amr)

Conditions

UNC45B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.7
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0172% Admixed American · 10/58,238 alleles

Filtering AF 0.00925% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.007%

Overall 0.00714% 114/1,596,180 alleles · ultra-rare exomes 103/1,444,050 · genomes 11/152,130 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0172%	5,824
East Asian	0.0116%	8,622
Remaining individualsnot grpmax-eligible	0.0113%	8,814
European (non-Finnish)	0.00726%	13,772
African / African-American	0.00675%	14,808
Finnishnot grpmax-eligible	0.00157%	63,790
South Asian	0.00113%	88,644

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: UNC45B
Protein: p.Arg434=
Coding: c.1302C>T
MANE Select: NM_001267052
dbSNP: rs113010242
Type: single nucleotide variant
Location: chr17:35168211 (GRCh38)
Gene constraint: LOEUF 0.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.38

Full UNC45B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UNC45B-related disorder

Similar variants

UNC45B p.Arg434Cys Uncertain significance ★ ⚠ same residue
UNC45B p.Arg434His Uncertain significance ★ ⚠ same residue
UNC45B p.Arg752Gln Pathogenic ★★ same condition
UNC45B p.Ala597Thr Uncertain significance ★ ⚠ same condition
UNC45B p.Ala700Asp Uncertain significance ★ ⚠ same condition
UNC45B p.Leu538Phe Uncertain significance ★ ⚠ same condition
UNC45B p.Lys834Arg Uncertain significance ★ ⚠ same condition
UNC45B p.Ile331Asn 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/unc45b-p-arg434 (accessed [today's date]).

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