Is UTP4 p.Ser177= (c.531C>T) pathogenic?

UTP4 p.Ser177= (c.531C>T) is classified Conflicting classifications of pathogenicity in UTP4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-03). Very rare (popmax 0.0022%, sas); Associated with hereditary North American Indian childhood cirrhosis.

What condition is associated with UTP4 p.Ser177= (c.531C>T)?

UTP4 p.Ser177= (c.531C>T) is associated with hereditary North American Indian childhood cirrhosis (ClinVar).

How common is UTP4 p.Ser177= (c.531C>T) in the general population?

UTP4 p.Ser177= (c.531C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

How is Progressive familial intrahepatic cholestasis inherited?

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

UTP4 p.Ser177=

c.531C>T · rs370682701 · VCV887044

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.3	GERP -5.2
Overall
CADD	2.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00161% 26/1,613,886 alleles · very rare exomes 23/1,461,692 · genomes 3/152,194 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,543
European (non-Finnish)	0.00203%	49,161

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.Ser177=
Coding: c.531C>T
MANE Select: NM_032830
dbSNP: rs370682701
Type: single nucleotide variant
Location: chr16:69143182 (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

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-ser177 (accessed [today's date]).

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