Is UTP14C p.Arg543Gln (c.1628G>A) pathogenic?

UTP14C p.Arg543Gln (c.1628G>A) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-01). AlphaMissense: likely benign (0.0602); Ultra-rare (popmax 0.0713%, eas).

How common is UTP14C p.Arg543Gln (c.1628G>A) in the general population?

UTP14C p.Arg543Gln (c.1628G>A) is ultra-rare (popmax 0.0713%, eas) (gnomAD).

What do computational predictors say about UTP14C p.Arg543Gln (c.1628G>A)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

UTP14C p.Arg543Gln

c.1628G>A · VCV3814513

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0713%, eas)

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	0.0602	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -5.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.57	GERP -3.4
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	0.789	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 0.0713% East Asian · 32/44,892 alleles

Filtering AF 0.0519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0452%

Overall 0.00576% 93/1,614,044 alleles · ultra-rare exomes 83/1,461,892 · genomes 10/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0713%	1,403
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00667%	14,982
Finnishnot grpmax-eligible	0.00468%	21,347
South Asian	0.00439%	22,770
European (non-Finnish)	0.00339%	29,501
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Admixed American	0.00167%	60,000

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.Arg543Gln
Coding: c.1628G>A
MANE Select: NM_021645
Type: single nucleotide variant
Location: chr13:52030432 (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-arg543gln (accessed [today's date]).

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