Is UNC45A p.Asp381Glu (c.1143C>G) pathogenic?

UNC45A p.Asp381Glu (c.1143C>G) is classified Uncertain significance in UNC45A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely pathogenic (0.8893); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with UNC45A p.Asp381Glu (c.1143C>G)?

UNC45A p.Asp381Glu (c.1143C>G) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45A p.Asp381Glu (c.1143C>G) in the general population?

UNC45A p.Asp381Glu (c.1143C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC45A p.Asp381Glu (c.1143C>G)?

AlphaMissense predicts likely pathogenic (score 0.8893) — an in-silico prediction, not a clinical call.

UNC45A p.Asp381Glu

c.1143C>G · VCV4634114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8893 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8893	likely pathogenic
REVEL	0.343	indeterminate
SaProt	LLR -5.75	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP 0.87, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	21.3	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

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: UNC45A
Protein: p.Asp381Glu
Coding: c.1143C>G
MANE Select: NM_018671
Type: single nucleotide variant
Location: chr15:90945007 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 381: a UniProt-annotated variant site (in oohe; uncertain significance)

Full UNC45A 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

UNC45A p.Asp381Tyr Uncertain significance ★ ⚠ same residue
UNC45A p.Asp381Val Uncertain significance ★ ⚠ same residue
UNC45A p.Ala214Val Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala371Thr Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala386Val Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala428Thr Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala592Val Uncertain significance ★★ ⚠ same condition
UNC45A p.Ala711Thr 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/unc45a-p-asp381glu (accessed [today's date]).

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