Is UNC45B p.Ser403Pro (c.1207T>C) pathogenic?

UNC45B p.Ser403Pro (c.1207T>C) is classified Uncertain significance in UNC45B (ClinVar, Single submitter, 2 submitters; last evaluated 2020-06-12). AlphaMissense: likely pathogenic (0.9828); No allele count reported in gnomAD v4.1 (AN 1,585,964); Associated with myofibrillar myopathy 11.

What condition is associated with UNC45B p.Ser403Pro (c.1207T>C)?

UNC45B p.Ser403Pro (c.1207T>C) is associated with myofibrillar myopathy 11, cataract 43 (ClinVar).

How common is UNC45B p.Ser403Pro (c.1207T>C) in the general population?

UNC45B p.Ser403Pro (c.1207T>C) is no allele count reported in gnomAD v4.1 (AN 1,585,964) (gnomAD).

What do computational predictors say about UNC45B p.Ser403Pro (c.1207T>C)?

AlphaMissense predicts likely pathogenic (score 0.9828) — an in-silico prediction, not a clinical call.

UNC45B p.Ser403Pro

c.1207T>C · rs2092154042 · VCV996753

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9828 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,585,964)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

myofibrillar myopathy 11

Computational evidence

Protein change
AlphaMissense	0.9828	likely pathogenic · top 6% in UNC45B
REVEL	0.466	indeterminate
SaProt	LLR -14.11	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 38 kb · p 0.24 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,585,964). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: UNC45B
Protein: p.Ser403Pro
Coding: c.1207T>C
MANE Select: NM_001267052
dbSNP: rs2092154042
Type: single nucleotide variant
Location: chr17:35168116 (GRCh38)
Gene constraint: LOEUF 0.969 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.38
Residue 403: a UniProt-annotated variant site (in mfm11; mislocated away from the a-band to the z-disk)

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

Also linked: cataract 43

Similar variants

UNC45B p.Ser403Leu 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.Ala737Ser Uncertain significance ★ ⚠ same condition
UNC45B p.Arg776Trp Conflicting classifications of pathogenicity ★ ⚠ 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-ser403pro (accessed [today's date]).

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