Is UTP14C p.Arg58Trp (c.172C>T) pathogenic?

UTP14C p.Arg58Trp (c.172C>T) is classified Uncertain significance in UTP14C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-08). AlphaMissense: likely benign (0.0652); Ultra-rare (popmax 0.0824%, eas); Associated with ALG11-congenital disorder of glycosylation.

What condition is associated with UTP14C p.Arg58Trp (c.172C>T)?

UTP14C p.Arg58Trp (c.172C>T) is associated with ALG11-congenital disorder of glycosylation (ClinVar).

How common is UTP14C p.Arg58Trp (c.172C>T) in the general population?

UTP14C p.Arg58Trp (c.172C>T) is ultra-rare (popmax 0.0824%, eas) (gnomAD).

How is ALG11-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about UTP14C p.Arg58Trp (c.172C>T)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

UTP14C p.Arg58Trp

c.172C>T · rs184583544 · VCV883177

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0824%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ALG11-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.3
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	6.713	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 0.0824% East Asian · 37/44,890 alleles

Filtering AF 0.0614% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00489% 79/1,614,172 alleles · ultra-rare exomes 69/1,461,888 · genomes 10/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0824%	1,213
South Asian	0.00439%	22,770
European (non-Finnish)	0.00297%	33,715
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-American	0.00133%	75,044

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.Arg58Trp
Coding: c.172C>T
MANE Select: NM_021645
dbSNP: rs184583544
Type: single nucleotide variant
Location: chr13:52028976 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.59

Full UTP14C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG11-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG11-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ALG11 p.Met395Thr Likely pathogenic ★★ same condition
ALG11 p.Arg346Cys Uncertain significance ★★ ⚠ same condition
UTP14C p.Val157Gly Uncertain significance ★★ ⚠ same condition
ALG11 c.*468G>T Benign ★★ same condition
ALG11 c.*148A>T Uncertain significance ★ same condition
ALG11 c.*490C>T Uncertain significance ★ same condition
ALG11 c.*491G>A Uncertain significance ★ ⚠ same condition
ALG11 c.*953A>G Uncertain significance ★ ⚠ same condition

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-arg58trp (accessed [today's date]).

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