Is UNC45B p.Val484Ala (c.1451T>C) pathogenic?

UNC45B p.Val484Ala (c.1451T>C) is classified Uncertain significance in UNC45B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely pathogenic (0.8759); Ultra-rare (popmax 0.0747%, afr); Associated with Inborn genetic diseases.

What condition is associated with UNC45B p.Val484Ala (c.1451T>C)?

UNC45B p.Val484Ala (c.1451T>C) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45B p.Val484Ala (c.1451T>C) in the general population?

UNC45B p.Val484Ala (c.1451T>C) is ultra-rare (popmax 0.0747%, afr) (gnomAD).

What do computational predictors say about UNC45B p.Val484Ala (c.1451T>C)?

AlphaMissense predicts likely pathogenic (score 0.8759) — an in-silico prediction, not a clinical call.

UNC45B p.Val484Ala

c.1451T>C · rs143843347 · VCV2373720

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8759 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0747%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8759	likely pathogenic
REVEL	0.584	indeterminate
SaProt	LLR -10.24	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	27.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0747% African / African-American · 50/66,952 alleles

Filtering AF 0.0581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0523%

Overall 0.0038% 51/1,341,424 alleles · ultra-rare exomes 17/1,189,236 · genomes 34/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0747%	1,339
Remaining individualsnot grpmax-eligible	0.00201%	49,842

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.Val484Ala
Coding: c.1451T>C
MANE Select: NM_001267052
dbSNP: rs143843347
Type: single nucleotide variant
Location: chr17:35168360 (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.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
UNC45B p.Gln400His 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-val484ala (accessed [today's date]).

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