Is UTP14C p.Lys306Glu (c.916A>G) pathogenic?

UTP14C p.Lys306Glu (c.916A>G) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.3619); Ultra-rare (popmax 0.0137%, nfe).

How common is UTP14C p.Lys306Glu (c.916A>G) in the general population?

UTP14C p.Lys306Glu (c.916A>G) is ultra-rare (popmax 0.0137%, nfe) (gnomAD).

What do computational predictors say about UTP14C p.Lys306Glu (c.916A>G)?

AlphaMissense predicts ambiguous (score 0.3619) — an in-silico prediction, not a clinical call.

UTP14C p.Lys306Glu

c.916A>G · VCV4603250

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3619 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0137%, nfe)

⚠ 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	0.3619	ambiguous
REVEL	0.32	indeterminate
SaProt	LLR -13.12	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.7	GERP 1.9, 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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0137% European (non-Finnish) · 162/1,180,060 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.0102% 164/1,614,144 alleles · ultra-rare exomes 157/1,461,892 · genomes 7/152,252 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0137%	7,284
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	74,948

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.Lys306Glu
Coding: c.916A>G
MANE Select: NM_021645
Type: single nucleotide variant
Location: chr13:52029720 (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-lys306glu (accessed [today's date]).

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