Is UNC45A p.Gly343Val (c.1028G>T) pathogenic?

UNC45A p.Gly343Val (c.1028G>T) is classified Pathogenic in UNC45A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-06-09). AlphaMissense: likely pathogenic (0.9313); Absent from gnomAD v4.1; Associated with osteootohepatoenteric syndrome.

What condition is associated with UNC45A p.Gly343Val (c.1028G>T)?

UNC45A p.Gly343Val (c.1028G>T) is associated with osteootohepatoenteric syndrome (ClinVar).

How common is UNC45A p.Gly343Val (c.1028G>T) in the general population?

UNC45A p.Gly343Val (c.1028G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC45A p.Gly343Val (c.1028G>T)?

AlphaMissense predicts likely pathogenic (score 0.9313) — an in-silico prediction, not a clinical call.

UNC45A p.Gly343Val

c.1028G>T · rs2036482593 · VCV1164087

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9313 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteootohepatoenteric syndrome

Computational evidence

Protein change
AlphaMissense	0.9313	likely pathogenic ✓ concordant with ClinVar
REVEL	0.648	pathogenic-leaning
SaProt	LLR -14.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.39	acceptor gain · deltas
Pangolin	Δ0.41	loss · gain 0.32 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	34.0	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.Gly343Val
Coding: c.1028G>T
MANE Select: NM_018671
dbSNP: rs2036482593
Type: single nucleotide variant
Location: chr15:90944892 (GRCh38)
Gene constraint: LOEUF 0.885 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.36 · 1 PDB
Residue 343: 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

osteootohepatoenteric syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC45A p.Gly343= Likely benign ★ same residue
UNC45A p.Met723Ile Uncertain significance ★★ ⚠ same condition
UNC45A c.1027+1G>A Likely pathogenic ★ same condition
UNC45A c.213+1G>C Likely pathogenic ★ same condition
UNC45A c.1500+1G>A Uncertain significance ★ same condition
UNC45A p.Ala40Asp Conflicting classifications of pathogenicity ★ ⚠ same condition
UNC45A p.Arg241Ter Uncertain significance ★ same condition
UNC45A p.Arg98Trp 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-gly343val (accessed [today's date]).

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