Is UTP14C p.Asp315Glu (c.945C>G) pathogenic?

UTP14C p.Asp315Glu (c.945C>G) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). AlphaMissense: likely pathogenic (0.6935); Rare (popmax 0.148%, mid).

How common is UTP14C p.Asp315Glu (c.945C>G) in the general population?

UTP14C p.Asp315Glu (c.945C>G) is rare (popmax 0.148%, mid) (gnomAD).

What do computational predictors say about UTP14C p.Asp315Glu (c.945C>G)?

AlphaMissense predicts likely pathogenic (score 0.6935) — an in-silico prediction, not a clinical call.

UTP14C p.Asp315Glu

c.945C>G · VCV3979086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6935 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

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	0.6935	likely pathogenic
REVEL	0.297	indeterminate
SaProt	LLR -11.87	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 -0.12
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	20.3	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 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0833% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0771%

Overall 0.00756% 122/1,614,174 alleles · rare exomes 119/1,461,886 · genomes 3/152,288 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.148%	674
South Asian	0.0999%	1,001
Remaining individualsnot grpmax-eligible	0.0096%	10,419
East Asian	0.00223%	44,880
European (non-Finnish)	0.00127%	78,670

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.Asp315Glu
Coding: c.945C>G
MANE Select: NM_021645
Type: single nucleotide variant
Location: chr13:52029749 (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-asp315glu (accessed [today's date]).

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