Is NR2E3 p.Pro214= (c.642C>G) pathogenic?

NR2E3 p.Pro214= (c.642C>G) is classified Likely benign in NR2E3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-30). Absent from gnomAD v4.1.

How common is NR2E3 p.Pro214= (c.642C>G) in the general population?

NR2E3 p.Pro214= (c.642C>G) is absent from gnomAD v4.1 (gnomAD).

NR2E3 p.Pro214=

c.642C>G · rs778657206 · VCV1573863

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.54	GERP -2.2, phastCons 0.026
Overall
CADD	2.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NR2E3
Protein: p.Pro214=
Coding: c.642C>G
MANE Select: NM_014249
dbSNP: rs778657206
Type: single nucleotide variant
Location: chr15:71812406 (GRCh38)
Gene constraint: LOEUF 1.47 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.59 · 1 PDB
Residue 214: the nr lbd domain; the 'disordered' region

Full NR2E3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NR2E3 p.Pro214Arg Uncertain significance ★★ ⚠ same residue
NR2E3 p.Pro214Leu Uncertain significance ★★ ⚠ same residue
NR2E3 p.Pro214Ser Uncertain significance ★★ ⚠ same residue
NR2E3 p.Pro214Ala Uncertain significance ★ ⚠ same residue
NR2E3 p.Pro214His Uncertain significance ★ ⚠ same residue
NR2E3 p.Pro214fs Pathogenic ★ same residue
NR2E3 c.118+1G>T Likely pathogenic ★★ same type
NR2E3 c.119-2A>C Pathogenic/Likely pathogenic ★★ 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/nr2e3-p-pro214 (accessed [today's date]).

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