Is UNC45B p.Ser228= (c.684C>T) pathogenic?

UNC45B p.Ser228= (c.684C>T) is classified Likely benign in UNC45B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-16). Absent from gnomAD v4.1.

How common is UNC45B p.Ser228= (c.684C>T) in the general population?

UNC45B p.Ser228= (c.684C>T) is absent from gnomAD v4.1 (gnomAD).

UNC45B p.Ser228=

c.684C>T · rs2508487173 · VCV2808694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP -0.21, phastCons 1
Overall
CADD	8.202	PHRED · no single calibrated threshold — expert panels disagree

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: UNC45B
Protein: p.Ser228=
Coding: c.684C>T
MANE Select: NM_001267052
dbSNP: rs2508487173
Type: single nucleotide variant
Location: chr17:35155340 (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.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
UNC45B p.Asp902Glu 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-ser228 (accessed [today's date]).

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