Is NR2C2 p.Arg235= (c.705A>G) pathogenic?

NR2C2 p.Arg235= (c.705A>G) is classified Likely benign in NR2C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-19). Very rare (popmax 0.00893%, eas).

How common is NR2C2 p.Arg235= (c.705A>G) in the general population?

NR2C2 p.Arg235= (c.705A>G) is very rare (popmax 0.00893%, eas) (gnomAD).

NR2C2 p.Arg235=

c.705A>G · VCV3921629

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00893%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.3	GERP 1.8, phastCons 1
Overall
CADD	16.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00893% East Asian · 4/44,812 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000497% 8/1,610,774 alleles · very rare exomes 7/1,458,414 · genomes 1/152,360 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00893%	11,203
South Asian	0.0033%	30,264
Remaining individualsnot grpmax-eligible	0.0016%	62,392

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: NR2C2
Protein: p.Arg235=
Coding: c.705A>G
MANE Select: NM_001291694
Type: single nucleotide variant
Location: chr3:15024115 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.50 · 5 PDB

Full NR2C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NR2C2 p.Thr224= Benign ★★ same type
NR2C2 c.72+1G>C Uncertain significance ★ same type
NR2C2 p.Ala319Val Uncertain significance ★ ⚠ same type
NR2C2 p.Ala59Thr Uncertain significance ★ ⚠ same type
NR2C2 p.Ala74Thr Uncertain significance ★ ⚠ same type
NR2C2 p.Arg101His Uncertain significance ★ ⚠ same type
NR2C2 p.Arg22His Uncertain significance ★ ⚠ same type
NR2C2 p.Arg254Cys 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/nr2c2-p-arg235 (accessed [today's date]).

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