Is UNC45B p.Arg367His (c.1100G>A) pathogenic?

UNC45B p.Arg367His (c.1100G>A) is classified Uncertain significance in UNC45B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.1818); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with UNC45B p.Arg367His (c.1100G>A)?

UNC45B p.Arg367His (c.1100G>A) is associated with Inborn genetic diseases (ClinVar).

How common is UNC45B p.Arg367His (c.1100G>A) in the general population?

UNC45B p.Arg367His (c.1100G>A) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about UNC45B p.Arg367His (c.1100G>A)?

AlphaMissense predicts likely benign (score 0.1818) — an in-silico prediction, not a clinical call.

UNC45B p.Arg367His

c.1100G>A · VCV3466030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1818 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1818	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -7.23	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 9.8	GERP 0.73, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	27.9	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 0.0107% African / African-American · 8/74,892 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00167% 27/1,613,710 alleles · ultra-rare exomes 21/1,461,558 · genomes 6/152,152 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,362
South Asian	0.00659%	15,175
Admixed American	0.00334%	29,977
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	0.000763%	131,100

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.Arg367His
Coding: c.1100G>A
MANE Select: NM_001267052
Type: single nucleotide variant
Location: chr17:35164115 (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.Arg367Cys Benign/Likely benign ★★ same residue
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

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-arg367his (accessed [today's date]).

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