Is UBTF p.Asp91His (c.271G>C) pathogenic?

UBTF p.Asp91His (c.271G>C) is classified Uncertain significance in UBTF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-05). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1.

How common is UBTF p.Asp91His (c.271G>C) in the general population?

UBTF p.Asp91His (c.271G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBTF p.Asp91His (c.271G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

UBTF p.Asp91His

c.271G>C · rs2509937333 · VCV2504358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -14.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 961 bp · p 1.8e-20 · regional, not allelic
Overall
CADD	29.9	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.Asp91His
Coding: c.271G>C
MANE Select: NM_014233
dbSNP: rs2509937333
Type: single nucleotide variant
Location: chr17:44215953 (GRCh38)

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

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-asp91his (accessed [today's date]).

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