Is UBTF p.Ser655Arg (c.1965C>G) pathogenic?

UBTF p.Ser655Arg (c.1965C>G) is classified Uncertain significance in UBTF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely pathogenic (0.9492); Very rare (popmax 0.00534%, afr); Associated with Inborn genetic diseases.

What condition is associated with UBTF p.Ser655Arg (c.1965C>G)?

UBTF p.Ser655Arg (c.1965C>G) is associated with Inborn genetic diseases (ClinVar).

How common is UBTF p.Ser655Arg (c.1965C>G) in the general population?

UBTF p.Ser655Arg (c.1965C>G) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about UBTF p.Ser655Arg (c.1965C>G)?

AlphaMissense predicts likely pathogenic (score 0.9492) — an in-silico prediction, not a clinical call.

UBTF p.Ser655Arg

c.1965C>G · VCV3977100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9492	likely pathogenic
REVEL	0.483	indeterminate
SaProt	LLR -5.21	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP -3.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 633 bp · p 0.14 · regional, not allelic
Overall
CADD	19.66	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 0.00534% African / African-American · 4/74,906 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000248% 4/1,614,070 alleles · very rare

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: UBTF
Protein: p.Ser655Arg
Coding: c.1965C>G
Type: single nucleotide variant
Location: chr17:44207759 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-ser655arg (accessed [today's date]).

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