Is NIT2 p.Arg210Trp (c.628C>T) pathogenic?

NIT2 p.Arg210Trp (c.628C>T) is classified Uncertain significance in NIT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.3662); Very rare (popmax 0.00769%, sas).

How common is NIT2 p.Arg210Trp (c.628C>T) in the general population?

NIT2 p.Arg210Trp (c.628C>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about NIT2 p.Arg210Trp (c.628C>T)?

AlphaMissense predicts ambiguous (score 0.3662) — an in-silico prediction, not a clinical call.

NIT2 p.Arg210Trp

c.628C>T · VCV3919903

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3662 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Computational evidence

Protein change
AlphaMissense	0.3662	ambiguous
REVEL	0.575	indeterminate
SaProt	LLR -17.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -0.047, phastCons 0.98
Regional constraint	o/e 0.90	unconstrained · MANE · 20 kb · p 0.07 · regional, not allelic
Overall
CADD	32.0	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 0.00769% South Asian · 7/91,062 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00112% 18/1,613,388 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,009
African / African-American	0.00267%	37,460
Remaining individualsnot grpmax-eligible	0.0016%	62,432
European (non-Finnish)	0.000678%	147,448

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: NIT2
Protein: p.Arg210Trp
Coding: c.628C>T
MANE Select: NM_020202
Type: single nucleotide variant
Location: chr3:100352447 (GRCh38)
Gene constraint: LOEUF 1.249 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.62
Residue 210: the cn hydrolase domain

Full NIT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NIT2 p.Ala209Val Uncertain significance ★ ⚠ same type
NIT2 p.Ala51Gly Uncertain significance ★ ⚠ same type
NIT2 p.Ala51Val Uncertain significance ★ ⚠ same type
NIT2 p.Arg157Gln Uncertain significance ★ ⚠ same type
NIT2 p.Arg195Trp Uncertain significance ★ ⚠ same type
NIT2 p.Arg23Cys Uncertain significance ★ ⚠ same type
NIT2 p.Arg255Cys Uncertain significance ★ ⚠ same type
NIT2 p.Arg29Trp 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/nit2-p-arg210trp (accessed [today's date]).

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