Is UNC45B p.Val792Ile (c.2374G>A) pathogenic?

UNC45B p.Val792Ile (c.2374G>A) is classified Uncertain significance in UNC45B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). AlphaMissense: likely benign (0.121); Ultra-rare (popmax 0.0161%, eas); Associated with myofibrillar myopathy 11.

What condition is associated with UNC45B p.Val792Ile (c.2374G>A)?

UNC45B p.Val792Ile (c.2374G>A) is associated with myofibrillar myopathy 11 (ClinVar).

How common is UNC45B p.Val792Ile (c.2374G>A) in the general population?

UNC45B p.Val792Ile (c.2374G>A) is ultra-rare (popmax 0.0161%, eas) (gnomAD).

What do computational predictors say about UNC45B p.Val792Ile (c.2374G>A)?

AlphaMissense predicts likely benign (score 0.121) — an in-silico prediction, not a clinical call.

UNC45B p.Val792Ile

c.2374G>A · VCV3775861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.121 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0161%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 11

Computational evidence

Protein change
AlphaMissense	0.121	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -7.39	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 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	25.2	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V794I vs ClinVar V792I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0161% East Asian · 7/43,450 alleles

Filtering AF 0.00747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00528%

Overall 0.000701% 11/1,568,068 alleles · ultra-rare exomes 9/1,416,000 · genomes 2/152,068 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0161%	6,207
Admixed American	0.00373%	26,789
Remaining individualsnot grpmax-eligible	0.00166%	60,306
European (non-Finnish)	8.64e-05%	1,157,044

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.Val792Ile
Coding: c.2374G>A
MANE Select: NM_001267052
Type: single nucleotide variant
Location: chr17:35183427 (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

myofibrillar myopathy 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC45B p.Val792Leu Uncertain significance ★ same residue
UNC45B p.Arg752Gln Pathogenic ★★ same condition
UNC45B p.Asp496Val Uncertain significance ★★ ⚠ same condition
UNC45B c.808+39G>A Benign ★★ same condition
UNC45B c.2255+5G>C Likely pathogenic ★ same condition
UNC45B p.Ala25Thr Uncertain significance ★ ⚠ same condition
UNC45B p.Arg776Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
UNC45B p.Arg803Gln 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-val792ile (accessed [today's date]).

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