Is NR0B2 p.Ser142= (c.426C>T) pathogenic?

NR0B2 p.Ser142= (c.426C>T) is classified Likely benign in NR0B2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-22). Ultra-rare (popmax 0.0267%, amr); Associated with NR0B2-related disorder.

What condition is associated with NR0B2 p.Ser142= (c.426C>T)?

NR0B2 p.Ser142= (c.426C>T) is associated with NR0B2-related disorder (ClinVar).

How common is NR0B2 p.Ser142= (c.426C>T) in the general population?

NR0B2 p.Ser142= (c.426C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

NR0B2 p.Ser142=

c.426C>T · rs779114304 · VCV3045562

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

Conditions

NR0B2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,000 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00105% 17/1,613,318 alleles · ultra-rare exomes 17/1,461,074 · genomes 0/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,750
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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: NR0B2
Protein: p.Ser142=
Coding: c.426C>T
MANE Select: NM_021969
dbSNP: rs779114304
Type: single nucleotide variant
Location: chr1:26913515 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.42 · 14 PDB
Residue 142: the nr lbd domain

Full NR0B2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NR0B2-related disorder

Similar variants

NR0B2 p.Asp245Gly Uncertain significance ★★ ⚠ same condition
NR0B2 p.Ala209Thr Uncertain significance ★ ⚠ same condition
NR0B2 p.Ala31Thr Uncertain significance ★ ⚠ same condition
NR0B2 p.Arg257Gly Uncertain significance ★ ⚠ same condition
NR0B2 p.Arg34Pro Uncertain significance ★ ⚠ same condition
NR0B2 p.Arg86Gln Uncertain significance ★ ⚠ same condition
NR0B2 p.Ile240Val Uncertain significance ★ ⚠ same condition
NR0B2 p.Ala247Thr 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/nr0b2-p-ser142 (accessed [today's date]).

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