Is UTP18 p.Pro136Ser (c.406C>T) pathogenic?

UTP18 p.Pro136Ser (c.406C>T) is classified Uncertain significance in UTP18 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). AlphaMissense: likely benign (0.0672); Very rare (popmax 0.00407%, nfe).

How common is UTP18 p.Pro136Ser (c.406C>T) in the general population?

UTP18 p.Pro136Ser (c.406C>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

What do computational predictors say about UTP18 p.Pro136Ser (c.406C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

UTP18 p.Pro136Ser

c.406C>T · VCV3331712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -5.78	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 -0.015	GERP 0.002
Regional constraint	o/e 1.09	unconstrained · MANE · 36 kb · p 0.025 · regional, not allelic
Overall
CADD	7.929	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 0.00407% European (non-Finnish) · 48/1,180,032 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00316% 51/1,614,062 alleles · very rare exomes 50/1,461,846 · genomes 1/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,584
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Finnishnot grpmax-eligible	0.00156%	64,024

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: UTP18
Protein: p.Pro136Ser
Coding: c.406C>T
MANE Select: NM_016001
Type: single nucleotide variant
Location: chr17:51263337 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.92 · 3 PDB
Residue 136: the 'disordered' region

Full UTP18 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UTP18 p.Ala244Gly Uncertain significance ★ ⚠ same type
UTP18 p.Ala369Thr Uncertain significance ★ ⚠ same type
UTP18 p.Ala432Thr Uncertain significance ★ ⚠ same type
UTP18 p.Ala468Gly Uncertain significance ★ ⚠ same type
UTP18 p.Arg159Trp Uncertain significance ★ ⚠ same type
UTP18 p.Arg161Gln Uncertain significance ★ ⚠ same type
UTP18 p.Arg161Pro Uncertain significance ★ ⚠ same type
UTP18 p.Arg202Gln 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/utp18-p-pro136ser (accessed [today's date]).

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