Is UTP14C p.Pro440Ala (c.1318C>G) pathogenic?

UTP14C p.Pro440Ala (c.1318C>G) is classified Uncertain significance in UTP14C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-28). AlphaMissense: likely benign (0.0641); Absent from gnomAD v4.1.

How common is UTP14C p.Pro440Ala (c.1318C>G) in the general population?

UTP14C p.Pro440Ala (c.1318C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UTP14C p.Pro440Ala (c.1318C>G)?

AlphaMissense predicts likely benign (score 0.0641) — an in-silico prediction, not a clinical call.

UTP14C p.Pro440Ala

c.1318C>G · VCV3467394

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0641 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0641	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -5.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -0.16
Regional constraint	o/e 0.92	unconstrained · MANE · 2,297 bp · p 0.015 · regional, not allelic
Overall
CADD	4.209	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UTP14C
Protein: p.Pro440Ala
Coding: c.1318C>G
MANE Select: NM_021645
Type: single nucleotide variant
Location: chr13:52030122 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.59
Residue 440: the 'disordered' region

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

Similar variants

ALG11 p.Met395Thr Likely pathogenic ★★ same type
ALG11 p.Arg346Cys Uncertain significance ★★ ⚠ same type
UTP14C p.Arg58Trp Uncertain significance ★★ ⚠ same type
UTP14C p.Val157Gly Uncertain significance ★★ ⚠ same type
ALG11 c.*468G>T Benign ★★ same type
ALG11 c.*148A>T Uncertain significance ★ same type
ALG11 c.*490C>T Uncertain significance ★ same type
ALG11 c.*491G>A Uncertain significance ★ ⚠ same type

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-pro440ala (accessed [today's date]).

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