Is NTMT1 p.Ser45Phe (c.134C>T) pathogenic?

NTMT1 p.Ser45Phe (c.134C>T) is classified Uncertain significance in NTMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely pathogenic (0.9978); Absent from gnomAD v4.1.

How common is NTMT1 p.Ser45Phe (c.134C>T) in the general population?

NTMT1 p.Ser45Phe (c.134C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NTMT1 p.Ser45Phe (c.134C>T)?

AlphaMissense predicts likely pathogenic (score 0.9978) — an in-silico prediction, not a clinical call.

NTMT1 p.Ser45Phe

c.134C>T · VCV4559447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9978 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9978	likely pathogenic · top 1% in NTMT1
REVEL	0.757	pathogenic-leaning
SaProt	LLR -15.39	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 2,757 bp · p 2.2e-06 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: NTMT1
Protein: p.Ser45Phe
Coding: c.134C>T
MANE Select: NM_014064
Type: single nucleotide variant
Location: chr9:129632837 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 97.56 · 18 PDB
Residue 45: an α-helix

Full NTMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NTMT1 p.Ala65Thr Uncertain significance ★ ⚠ same type
NTMT1 p.Arg46Gln Uncertain significance ★ ⚠ same type
NTMT1 p.Arg46Trp Uncertain significance ★ ⚠ same type
NTMT1 p.Arg78Trp Uncertain significance ★ ⚠ same type
NTMT1 p.Asp95Val Uncertain significance ★ ⚠ same type
NTMT1 p.Gly29Ser Uncertain significance ★ ⚠ same type
NTMT1 p.Gly32Trp Uncertain significance ★ ⚠ same type
NTMT1 p.Gly69Arg 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/ntmt1-p-ser45phe (accessed [today's date]).

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