Is UNC45B p.Ala63Val (c.188C>T) pathogenic?

UNC45B p.Ala63Val (c.188C>T) is classified Uncertain significance in UNC45B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely benign (0.1346); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with UNC45B p.Ala63Val (c.188C>T)?

UNC45B p.Ala63Val (c.188C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45B p.Ala63Val (c.188C>T) in the general population?

UNC45B p.Ala63Val (c.188C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC45B p.Ala63Val (c.188C>T)?

AlphaMissense predicts likely benign (score 0.1346) — an in-silico prediction, not a clinical call.

UNC45B p.Ala63Val

c.188C>T · VCV3977726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1346 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1346	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -4.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1.3, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	22.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UNC45B
Protein: p.Ala63Val
Coding: c.188C>T
MANE Select: NM_001267052
Type: single nucleotide variant
Location: chr17:35148992 (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-ala63val (accessed [today's date]).

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