Is UBTF p.Pro664= (c.1992C>T) pathogenic?

UBTF p.Pro664= (c.1992C>T) is classified Likely benign in UBTF (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). Ultra-rare (popmax 0.0699%, nfe).

How common is UBTF p.Pro664= (c.1992C>T) in the general population?

UBTF p.Pro664= (c.1992C>T) is ultra-rare (popmax 0.0699%, nfe) (gnomAD).

UBTF p.Pro664=

c.1992C>T · VCV4935365

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0699%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.71	GERP -0.91, phastCons 1
Overall
CADD	8.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0699% European (non-Finnish) · 825/1,180,032 alleles

Filtering AF 0.0659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0643%

Overall 0.0554% 895/1,614,166 alleles · ultra-rare exomes 837/1,461,894 · genomes 58/152,272 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0699%	1,430
Remaining individualsnot grpmax-eligible	0.0688%	1,454
Admixed American	0.0167%	6,002
African / African-American	0.012%	8,335
Finnishnot grpmax-eligible	0.00625%	16,010
South Asian	0.00439%	22,772

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.Pro664=
Coding: c.1992C>T
MANE Select: NM_014233
Type: single nucleotide variant
Location: chr17:44207732 (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-pro664 (accessed [today's date]).

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