Is UNC45B p.Arg367Cys (c.1099C>T) pathogenic?

UNC45B p.Arg367Cys (c.1099C>T) is classified Benign/Likely benign in UNC45B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-04). AlphaMissense: likely benign (0.2069); Low-frequency (popmax 4.61%, afr).

How common is UNC45B p.Arg367Cys (c.1099C>T) in the general population?

UNC45B p.Arg367Cys (c.1099C>T) is low-frequency (popmax 4.61%, afr) (gnomAD).

What do computational predictors say about UNC45B p.Arg367Cys (c.1099C>T)?

AlphaMissense predicts likely benign (score 0.2069) — an in-silico prediction, not a clinical call.

UNC45B p.Arg367Cys

c.1099C>T · rs116362062 · VCV777160

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2069 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.61%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2069	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.34	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 5.9	GERP 0.63, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	27.7	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

Grpmax group 4.61% African / African-American · 3,453/74,982 alleles

Filtering AF 4.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.42%

Overall 0.26% 4,200/1,613,818 alleles · low-frequency exomes 2,146/1,461,574 · genomes 2,054/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.61%	22
Admixed American	0.507%	197
Remaining individualsnot grpmax-eligible	0.31%	322
Middle Eastern	0.198%	505
East Asian	0.0245%	4,076
European (non-Finnish)	0.0177%	5,645
South Asian	0.0154%	6,503
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,865

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.Arg367Cys
Coding: c.1099C>T
MANE Select: NM_001267052
dbSNP: rs116362062
Type: single nucleotide variant
Location: chr17:35164114 (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

Similar variants

UNC45B p.Arg367His Uncertain significance ★ ⚠ same residue
UNC45B p.Arg752Gln Pathogenic ★★ same type
UNC45B p.Ala626Gly Uncertain significance ★★ ⚠ same type
UNC45B p.Arg481Cys Uncertain significance ★★ ⚠ same type
UNC45B p.Arg622Gln Uncertain significance ★★ ⚠ same type
UNC45B p.Arg713Gly Uncertain significance ★★ ⚠ same type
UNC45B p.Arg752Trp Uncertain significance ★★ ⚠ same type
UNC45B p.Asp496Val Uncertain significance ★★ ⚠ same type

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-arg367cys (accessed [today's date]).

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