Is UTP14C p.His222Asp (c.664C>G) pathogenic?

UTP14C p.His222Asp (c.664C>G) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-30). AlphaMissense: likely pathogenic (0.5648); Ultra-rare (popmax 0.0164%, mid).

How common is UTP14C p.His222Asp (c.664C>G) in the general population?

UTP14C p.His222Asp (c.664C>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about UTP14C p.His222Asp (c.664C>G)?

AlphaMissense predicts likely pathogenic (score 0.5648) — an in-silico prediction, not a clinical call.

UTP14C p.His222Asp

c.664C>G · rs749546864 · VCV2516718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

2/3 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	0.5648	likely pathogenic
REVEL	0.071	moderately benign-leaning
SaProt	LLR -11.83	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.7	GERP -0.11, phastCons 0.055
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	17.6	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000991% 16/1,614,080 alleles · ultra-rare exomes 13/1,461,894 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
South Asian	0.00878%	11,386
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000508%	196,674

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.His222Asp
Coding: c.664C>G
MANE Select: NM_021645
dbSNP: rs749546864
Type: single nucleotide variant
Location: chr13:52029468 (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-his222asp (accessed [today's date]).

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