Is UBTF p.Lys533= (c.1599G>A) pathogenic?

UBTF p.Lys533= (c.1599G>A) is classified Benign in UBTF (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-07-16). Common (popmax 66%, eas) — too common for a highly-penetrant pathogenic allele.

UBTF p.Lys533=

Q: How common is UBTF p.Lys533= (c.1599G>A) in the general population?

UBTF p.Lys533= (c.1599G>A) is common (popmax 66%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1599G>A · rs2071167 · VCV1220958

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 66%, eas) — too common for a highly-penetrant pathogenic allele

⚠ 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
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 0.59	GERP -1.3, phastCons 0.96
Overall
CADD	9.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 66% East Asian · 29,618/44,872 alleles

Filtering AF 65.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 65.1%

Overall 27.9% 449,873/1,613,966 alleles · common exomes 394,581/1,461,848 · genomes 55,292/152,118 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	66%	2
African / African-American	55%	2
Ashkenazi Jewishnot grpmax-eligible	37.7%	3
Admixed American	34.4%	3
Middle Eastern	31.5%	3
Remaining individualsnot grpmax-eligible	31.1%	3
Finnishnot grpmax-eligible	26.4%	4
Amishnot grpmax-eligible	26%	4
European (non-Finnish)	24.3%	4
South Asian	24.2%	4

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.Lys533=
Coding: c.1599G>A
MANE Select: NM_014233
dbSNP: rs2071167
Type: single nucleotide variant
Location: chr17:44210151 (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-lys533 (accessed [today's date]).

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