Is UBTF p.Leu618= (c.1852C>T) pathogenic?

UBTF p.Leu618= (c.1852C>T) is classified Likely benign in UBTF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-15). Ultra-rare (popmax 0.025%, amr).

How common is UBTF p.Leu618= (c.1852C>T) in the general population?

UBTF p.Leu618= (c.1852C>T) is ultra-rare (popmax 0.025%, amr) (gnomAD).

UBTF p.Leu618=

c.1852C>T · VCV4887240

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.025%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -2.4, phastCons 1
Overall
CADD	7.846	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.025% Admixed American · 15/59,994 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0124%

Overall 0.0013% 21/1,613,876 alleles · ultra-rare exomes 16/1,461,684 · genomes 5/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.025%	4,000
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	0.000424%	235,981

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.Leu618=
Coding: c.1852C>T
MANE Select: NM_014233
Type: single nucleotide variant
Location: chr17:44209405 (GRCh38)
Gene constraint: LOEUF 0.133 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 4 PDB
Residue 618: a DNA-binding region

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

Similar variants

UBTF c.59-143C>T Benign ★★ same type
UBTF p.Arg218Gln Uncertain significance ★ ⚠ same type
UBTF p.Asp738Asn Uncertain significance ★ ⚠ same type
UBTF p.Gly479Ser Uncertain significance ★ ⚠ same type
UBTF p.Lys616Arg Uncertain significance ★ ⚠ same type
UBTF p.Met27Ile Uncertain significance ★ ⚠ same type
UBTF p.Asp696= Likely benign ★ same type
UBTF p.Ser758= Likely benign ★ same type

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-leu618 (accessed [today's date]).

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