Is NR0B2 p.Pro18= (c.54C>T) pathogenic?

NR0B2 p.Pro18= (c.54C>T) is classified Likely benign in NR0B2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-07-29). Very rare (popmax 0.00695%, amr).

How common is NR0B2 p.Pro18= (c.54C>T) in the general population?

NR0B2 p.Pro18= (c.54C>T) is very rare (popmax 0.00695%, amr) (gnomAD).

NR0B2 p.Pro18=

c.54C>T · rs780830830 · VCV3034559

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00695%, amr)

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 -12	GERP -4
Overall
CADD	0.249	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00695% Admixed American · 3/43,146 alleles

Filtering AF 0.00184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000911%

Overall 0.000874% 13/1,487,868 alleles · very rare exomes 13/1,335,544 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00695%	14,382
African / African-American	0.0028%	35,707
Remaining individualsnot grpmax-eligible	0.00175%	57,118
European (non-Finnish)	0.000627%	159,575

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.Pro18=
Coding: c.54C>T
MANE Select: NM_021969
dbSNP: rs780830830
Type: single nucleotide variant
Location: chr1:26913887 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.42 · 14 PDB
Residue 18: the nr lbd domain

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

Similar variants

NR0B2 p.Ala145Val Uncertain significance ★★ ⚠ same type
NR0B2 p.Arg238Cys Uncertain significance ★★ ⚠ same type
NR0B2 p.Arg54Cys Uncertain significance ★★ ⚠ same type
NR0B2 p.Arg71Gly Uncertain significance ★★ ⚠ same type
NR0B2 p.Arg86Trp Uncertain significance ★★ ⚠ same type
NR0B2 p.Asp245Gly Uncertain significance ★★ ⚠ same type
NR0B2 p.Gln84Glu Uncertain significance ★★ ⚠ same type
NR0B2 p.Leu118Val 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/nr0b2-p-pro18 (accessed [today's date]).

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