Is NAT10 p.Phe96Ser (c.287T>C) pathogenic?

NAT10 p.Phe96Ser (c.287T>C) is classified Uncertain significance in NAT10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.994); Absent from gnomAD v4.1.

How common is NAT10 p.Phe96Ser (c.287T>C) in the general population?

NAT10 p.Phe96Ser (c.287T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NAT10 p.Phe96Ser (c.287T>C)?

AlphaMissense predicts likely pathogenic (score 0.994) — an in-silico prediction, not a clinical call.

NAT10 p.Phe96Ser

c.287T>C · rs2496160777 · VCV2613700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.994	likely pathogenic · top 5% in NAT10
REVEL	0.853	moderately pathogenic-leaning
SaProt	LLR -14.58	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 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.025 · regional, not allelic
Overall
CADD	28.3	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.Phe96Ser
Coding: c.287T>C
MANE Select: NM_024662
dbSNP: rs2496160777
Type: single nucleotide variant
Location: chr11:34112138 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.61 · 4 PDB

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-phe96ser (accessed [today's date]).

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