Is NIT1 p.His307Arg (c.920A>G) pathogenic?

NIT1 p.His307Arg (c.920A>G) is classified Uncertain significance in NIT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-30). AlphaMissense: likely benign (0.095); Very rare (popmax 0.00314%, nfe).

How common is NIT1 p.His307Arg (c.920A>G) in the general population?

NIT1 p.His307Arg (c.920A>G) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about NIT1 p.His307Arg (c.920A>G)?

AlphaMissense predicts likely benign (score 0.095) — an in-silico prediction, not a clinical call.

NIT1 p.His307Arg

c.920A>G · rs532171421 · VCV2219869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.095 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.095	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.5, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,585 bp · p 0.18 · regional, not allelic
Overall
CADD	18.53	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00314% European (non-Finnish) · 37/1,180,026 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00229% 37/1,613,648 alleles · very rare exomes 37/1,461,358 · genomes 0/152,290 · joint denominator

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: NIT1
Protein: p.His307Arg
Coding: c.920A>G
MANE Select: NM_005600
dbSNP: rs532171421
Type: single nucleotide variant
Location: chr1:161120701 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.57

Full NIT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NIT1 c.591+2T>G Likely pathogenic ★ same type
DEDD p.Arg261Leu Uncertain significance ★ ⚠ same type
NIT1 p.Ala117Thr Uncertain significance ★ ⚠ same type
NIT1 p.Ala236Thr Uncertain significance ★ ⚠ same type
NIT1 p.Ala68Val Uncertain significance ★ ⚠ same type
NIT1 p.Ala74Pro Uncertain significance ★ ⚠ same type
NIT1 p.Ala79Gly Uncertain significance ★ ⚠ same type
NIT1 p.Arg207Gln 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/nit1-p-his307arg (accessed [today's date]).

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