Is NR0B1 p.Ile320Phe (c.958A>T) pathogenic?

NR0B1 p.Ile320Phe (c.958A>T) is classified Uncertain significance in NR0B1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely benign (0.2404); Very rare (popmax 0.000112%, nfe); Associated with Inborn genetic diseases.

What condition is associated with NR0B1 p.Ile320Phe (c.958A>T)?

NR0B1 p.Ile320Phe (c.958A>T) is associated with Inborn genetic diseases (ClinVar).

How common is NR0B1 p.Ile320Phe (c.958A>T) in the general population?

NR0B1 p.Ile320Phe (c.958A>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about NR0B1 p.Ile320Phe (c.958A>T)?

AlphaMissense predicts likely benign (score 0.2404) — an in-silico prediction, not a clinical call.

NR0B1 p.Ile320Phe

c.958A>T · VCV3880855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2404 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2404	likely benign
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -4.68	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP 0.5, phastCons 0.2
Regional constraint	o/e 0.95	unconstrained · MANE · 1,073 bp · p 0.37 · regional, not allelic
Overall
CADD	19.84	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 0.000112% European (non-Finnish) · 1/892,282 alleles

Overall 8.29e-05% 1/1,205,625 alleles · very rare exomes 1/1,092,507 · genomes 0/113,118 · 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: NR0B1
Protein: p.Ile320Phe
Coding: c.958A>T
MANE Select: NM_000475
Type: single nucleotide variant
Location: chrX:30308406 (GRCh38)
Structure: AlphaFold pLDDT 60.48 · 1 PDB
Residue 320: the nr lbd domain

Full NR0B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NR0B1 p.Ile320Asn Uncertain significance ★ ⚠ same residue
NR0B1 p.Arg65Leu Uncertain significance ★★ ⚠ same condition
NR0B1 p.Glu428Asp Uncertain significance ★★ ⚠ same condition
NR0B1 p.Pro335His Uncertain significance ★★ ⚠ same condition
NR0B1 p.Pro345Gln Uncertain significance ★★ ⚠ same condition
NR0B1 p.Ala170Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
NR0B1 p.Ala292Val Uncertain significance ★ ⚠ same condition
NR0B1 p.Arg198His Uncertain significance ★ ⚠ same condition

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/nr0b1-p-ile320phe (accessed [today's date]).

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