Is NAT10 p.Arg900His (c.2699G>A) pathogenic?

NAT10 p.Arg900His (c.2699G>A) is classified Uncertain significance in NAT10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: ambiguous (0.5448); Very rare (popmax 0.00329%, sas).

How common is NAT10 p.Arg900His (c.2699G>A) in the general population?

NAT10 p.Arg900His (c.2699G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about NAT10 p.Arg900His (c.2699G>A)?

AlphaMissense predicts ambiguous (score 0.5448) — an in-silico prediction, not a clinical call.

NAT10 p.Arg900His

c.2699G>A · VCV4116902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5448 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
AlphaMissense	0.5448	ambiguous
REVEL	0.455	indeterminate
SaProt	LLR -10.51	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.025 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,062 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00118% 19/1,613,772 alleles · very rare exomes 16/1,461,800 · genomes 3/151,972 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,354
East Asian	0.00223%	44,882
African / African-American	0.00134%	74,820
European (non-Finnish)	0.00119%	84,286

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: NAT10
Protein: p.Arg900His
Coding: c.2699G>A
MANE Select: NM_024662
Type: single nucleotide variant
Location: chr11:34141195 (GRCh38)
Gene constraint: LOEUF 0.935 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.61 · 4 PDB
Residue 900: an α-helix; the 'required for localization to the nucleolus and midbody' region

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-arg900his (accessed [today's date]).

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