Is UTP14C p.Pro657Leu (c.1970C>T) pathogenic?

UTP14C p.Pro657Leu (c.1970C>T) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.0826); Very rare (popmax 0.00186%, nfe).

How common is UTP14C p.Pro657Leu (c.1970C>T) in the general population?

UTP14C p.Pro657Leu (c.1970C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about UTP14C p.Pro657Leu (c.1970C>T)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

UTP14C p.Pro657Leu

c.1970C>T · rs754040179 · VCV3187886

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ 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	0.0826	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -9.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	GERP -0.13, phastCons 0.034
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00186% European (non-Finnish) · 22/1,180,040 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00136% 22/1,614,036 alleles · very rare exomes 19/1,461,892 · genomes 3/152,144 · joint denominator

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.Pro657Leu
Coding: c.1970C>T
MANE Select: NM_021645
dbSNP: rs754040179
Type: single nucleotide variant
Location: chr13:52030774 (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-pro657leu (accessed [today's date]).

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