Is NAT10 p.Ser45Phe (c.134C>T) pathogenic?

NAT10 p.Ser45Phe (c.134C>T) is classified Uncertain significance in NAT10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-09). AlphaMissense: likely pathogenic (0.8767); Absent from gnomAD v4.1.

How common is NAT10 p.Ser45Phe (c.134C>T) in the general population?

NAT10 p.Ser45Phe (c.134C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NAT10 p.Ser45Phe (c.134C>T)?

AlphaMissense predicts likely pathogenic (score 0.8767) — an in-silico prediction, not a clinical call.

NAT10 p.Ser45Phe

c.134C>T · VCV3298463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8767 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8767	likely pathogenic
REVEL	0.521	indeterminate
SaProt	LLR -13.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
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 0.94	unconstrained · MANE · 38 kb · p 0.025 · regional, not allelic
Overall
CADD	25.4	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: NAT10
Protein: p.Ser45Phe
Coding: c.134C>T
MANE Select: NM_024662
Type: single nucleotide variant
Location: chr11:34108767 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.61 · 4 PDB
Residue 45: an α-helix

Full NAT10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NAT10 p.Asn132Asp Uncertain significance ★★ ⚠ same type
NAT10 c.2885+6G>C Benign ★★ same type
NAT10 c.373-7C>T Benign ★★ same type
NAT10 p.Ala983Thr Benign ★★ same type
NAT10 p.Gln203= Benign ★★ same type
NAT10 p.Pro224Leu Benign ★★ same type
NAT10 p.Pro562= Benign ★★ same type
NAT10 p.Thr153= Benign ★★ 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/nat10-p-ser45phe (accessed [today's date]).

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