Is UBTF p.Pro135Ser (c.403C>T) pathogenic?

UBTF p.Pro135Ser (c.403C>T) is classified Uncertain significance in UBTF (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-15). AlphaMissense: likely pathogenic (0.9992); Absent from gnomAD v4.1; Associated with childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder.

How common is UBTF p.Pro135Ser (c.403C>T) in the general population?

UBTF p.Pro135Ser (c.403C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBTF p.Pro135Ser (c.403C>T)?

AlphaMissense predicts likely pathogenic (score 0.9992) — an in-silico prediction, not a clinical call.

UBTF p.Pro135Ser

Q: What condition is associated with UBTF p.Pro135Ser (c.403C>T)?

UBTF p.Pro135Ser (c.403C>T) is associated with childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (ClinVar).

Q: How is Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.403C>T · rs2144550110 · VCV1330567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder

Computational evidence

Protein change
AlphaMissense	0.9992	likely pathogenic
REVEL	0.924	moderately pathogenic-leaning
SaProt	LLR -11.14	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 67 bp · p 2.3e-07 · regional, not allelic
Overall
CADD	32.0	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

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: UBTF
Protein: p.Pro135Ser
Coding: c.403C>T
dbSNP: rs2144550110
Type: single nucleotide variant
Location: chr17:44215725 (GRCh38)

Full UBTF gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Childhood-onset motor and cognitive regression syndrome with extrapyramidal movement disorder (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

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/ubtf-p-pro135ser (accessed [today's date]).

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