Is UTP4 p.Ala486= (c.1458C>T) pathogenic?

UTP4 p.Ala486= (c.1458C>T) is classified Likely benign in UTP4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-17). Ultra-rare (popmax 0.0813%, afr); Associated with UTP4-related disorder.

What condition is associated with UTP4 p.Ala486= (c.1458C>T)?

UTP4 p.Ala486= (c.1458C>T) is associated with UTP4-related disorder (ClinVar).

How common is UTP4 p.Ala486= (c.1458C>T) in the general population?

UTP4 p.Ala486= (c.1458C>T) is ultra-rare (popmax 0.0813%, afr) (gnomAD).

UTP4 p.Ala486=

c.1458C>T · rs150828561 · VCV3046312

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, afr)

Conditions

UTP4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.1	GERP 1.1, phastCons 1
Overall
CADD	11.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0813% African / African-American · 61/75,040 alleles

Filtering AF 0.0649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.059%

Overall 0.0044% 71/1,613,880 alleles · ultra-rare exomes 29/1,461,626 · genomes 42/152,254 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0813%	1,230
Admixed American	0.0133%	7,501
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)	8.48e-05%	1,179,782

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: UTP4
Protein: p.Ala486=
Coding: c.1458C>T
MANE Select: NM_032830
dbSNP: rs150828561
Type: single nucleotide variant
Location: chr16:69160369 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.28 · 3 PDB

Full UTP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UTP4-related disorder

Similar variants

UTP4 p.Asn537Ser Uncertain significance ★★ ⚠ same condition
UTP4 p.Val522Met Uncertain significance ★★ ⚠ same condition
UTP4 p.Asn80His Uncertain significance ★ ⚠ same condition
UTP4 p.Phe311Leu Uncertain significance ★ ⚠ same condition
UTP4 p.Cys340Gly Uncertain significance same condition
UTP4 p.Cys520Tyr Uncertain significance ⚠ same condition
UTP4 p.Ile160Val Uncertain significance ⚠ same condition
UTP4 p.Pro649His Uncertain significance ⚠ same condition

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/utp4-p-ala486 (accessed [today's date]).

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