Is UTP4 p.Ala90= (c.270G>A) pathogenic?

UTP4 p.Ala90= (c.270G>A) is classified Benign in UTP4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-21). Low-frequency (popmax 1.49%, afr); Associated with hereditary North American Indian childhood cirrhosis.

What condition is associated with UTP4 p.Ala90= (c.270G>A)?

UTP4 p.Ala90= (c.270G>A) is associated with hereditary North American Indian childhood cirrhosis (ClinVar).

How common is UTP4 p.Ala90= (c.270G>A) in the general population?

UTP4 p.Ala90= (c.270G>A) is low-frequency (popmax 1.49%, afr) (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

UTP4 p.Ala90=

c.270G>A · rs16958656 · VCV887042

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.49%, afr)

Conditions

hereditary North American Indian childhood cirrhosis

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 -2.8	GERP -5.3
Overall
CADD	1.999	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.49% African / African-American · 1,116/75,042 alleles

Filtering AF 1.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.39%

Overall 0.124% 2,000/1,614,140 alleles · low-frequency exomes 1,300/1,461,846 · genomes 700/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.49%	67
Remaining individualsnot grpmax-eligible	0.122%	822
Admixed American	0.112%	896
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.0619%	1,614
South Asian	0.00659%	15,180

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.Ala90=
Coding: c.270G>A
MANE Select: NM_032830
dbSNP: rs16958656
Type: single nucleotide variant
Location: chr16:69136806 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.28 · 3 PDB
Residue 90: a turn

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

Disease context

hereditary North American Indian childhood cirrhosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Progressive familial intrahepatic cholestasis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy, Neonatal

Similar variants

UTP4 c.1287+6T>C Uncertain significance ★★ same condition
UTP4 c.1444+6A>C Uncertain significance ★★ same condition
UTP4 p.Arg291His Uncertain significance ★★ ⚠ same condition
UTP4 p.Arg417Trp Uncertain significance ★★ ⚠ same condition
UTP4 p.Asn537Ser Uncertain significance ★★ ⚠ same condition
UTP4 p.Gly459Glu Uncertain significance ★★ ⚠ same condition
UTP4 c.1164+8A>G Benign/Likely benign ★★ same condition
UTP4 c.1287+4A>G Benign/Likely benign ★★ 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-ala90 (accessed [today's date]).

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