Is UTP14C p.Leu627Pro (c.1880T>C) pathogenic?

UTP14C p.Leu627Pro (c.1880T>C) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely pathogenic (0.7231); Ultra-rare (popmax 0.0445%, eas).

How common is UTP14C p.Leu627Pro (c.1880T>C) in the general population?

UTP14C p.Leu627Pro (c.1880T>C) is ultra-rare (popmax 0.0445%, eas) (gnomAD).

What do computational predictors say about UTP14C p.Leu627Pro (c.1880T>C)?

AlphaMissense predicts likely pathogenic (score 0.7231) — an in-silico prediction, not a clinical call.

UTP14C p.Leu627Pro

c.1880T>C · rs748016111 · VCV2607867

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7231 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0445%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ 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
AlphaMissense	0.7231	likely pathogenic
REVEL	0.467	indeterminate
SaProt	LLR -12.31	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 5	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0445% East Asian · 20/44,896 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0246%

Overall 0.00149% 24/1,614,062 alleles · ultra-rare exomes 22/1,461,882 · genomes 2/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0445%	2,245
Remaining individualsnot grpmax-eligible	0.0064%	15,623

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: UTP14C
Protein: p.Leu627Pro
Coding: c.1880T>C
MANE Select: NM_021645
dbSNP: rs748016111
Type: single nucleotide variant
Location: chr13:52030684 (GRCh38)

Full UTP14C 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/utp14c-p-leu627pro (accessed [today's date]).

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