Is UNC45B p.Arg102Cys (c.304C>T) pathogenic?

UNC45B p.Arg102Cys (c.304C>T) is classified Uncertain significance in UNC45B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely benign (0.1969); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with UNC45B p.Arg102Cys (c.304C>T)?

UNC45B p.Arg102Cys (c.304C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45B p.Arg102Cys (c.304C>T) in the general population?

UNC45B p.Arg102Cys (c.304C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about UNC45B p.Arg102Cys (c.304C>T)?

AlphaMissense predicts likely benign (score 0.1969) — an in-silico prediction, not a clinical call.

UNC45B p.Arg102Cys

c.304C>T · VCV3466029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1969 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1969	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.66, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000434% 7/1,613,874 alleles · ultra-rare exomes 7/1,461,554 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,020
European (non-Finnish)	0.000254%	393,286

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.Arg102Cys
Coding: c.304C>T
MANE Select: NM_001267052
Type: single nucleotide variant
Location: chr17:35150146 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC45B p.Arg102His Uncertain significance ★ ⚠ same residue
UNC45B p.Ala626Gly Uncertain significance ★★ ⚠ same condition
UNC45B p.Arg481Cys Uncertain significance ★★ ⚠ same condition
UNC45B p.Arg622Gln Uncertain significance ★★ ⚠ same condition
UNC45B p.Arg713Gly Uncertain significance ★★ ⚠ same condition
UNC45B p.Arg752Trp Uncertain significance ★★ ⚠ same condition
UNC45B p.Asp902Glu Uncertain significance ★★ ⚠ same condition
UNC45B p.Cys84Phe 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-arg102cys (accessed [today's date]).

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