Is UNC45A p.Arg792Cys (c.2374C>T) pathogenic?

UNC45A p.Arg792Cys (c.2374C>T) is classified Uncertain significance in UNC45A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-10-13). AlphaMissense: likely benign (0.3315); Very rare (popmax 0.008%, afr); Associated with Inborn genetic diseases.

What condition is associated with UNC45A p.Arg792Cys (c.2374C>T)?

UNC45A p.Arg792Cys (c.2374C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45A p.Arg792Cys (c.2374C>T) in the general population?

UNC45A p.Arg792Cys (c.2374C>T) is very rare (popmax 0.008%, afr) (gnomAD).

What do computational predictors say about UNC45A p.Arg792Cys (c.2374C>T)?

AlphaMissense predicts likely benign (score 0.3315) — an in-silico prediction, not a clinical call.

UNC45A p.Arg792Cys

c.2374C>T · rs139226550 · VCV2170705

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3315 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.008%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3315	likely benign
REVEL	0.492	indeterminate
SaProt	LLR -9.79	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.5	GERP 0.67, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.36 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.008% African / African-American · 6/75,038 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00228%

Overall 0.00167% 27/1,613,582 alleles · very rare exomes 19/1,461,272 · genomes 8/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.008%	12,506
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00333%	30,013
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,254
European (non-Finnish)	0.0011%	90,772

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: UNC45A
Protein: p.Arg792Cys
Coding: c.2374C>T
MANE Select: NM_018671
dbSNP: rs139226550
Type: single nucleotide variant
Location: chr15:90952999 (GRCh38)

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

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-arg792cys (accessed [today's date]).

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