Is ENOX2 p.Pro490= (c.1470T>C) pathogenic?

ENOX2 p.Pro490= (c.1470T>C) is classified Benign in ENOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). Rare (popmax 0.274%, nfe).

How common is ENOX2 p.Pro490= (c.1470T>C) in the general population?

ENOX2 p.Pro490= (c.1470T>C) is rare (popmax 0.274%, nfe) (gnomAD).

ENOX2 p.Pro490=

c.1470T>C · rs143316789 · VCV719414

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.274%, nfe)

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 4.1	GERP -0.54, phastCons 1
Overall
CADD	9.702	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.274% European (non-Finnish) · 2,438/890,571 alleles

Filtering AF 0.265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.261%

Overall 0.247% 2,973/1,204,822 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.793%	126
European (non-Finnish)grpmax	0.274%	365
Remaining individualsnot grpmax-eligible	0.211%	474
Admixed American	0.0503%	1,988
South Asian	0.0388%	2,576
Ashkenazi Jewishnot grpmax-eligible	0.0273%	3,666
African / African-American	0.0245%	4,079
Middle Eastern	0.023%	4,343

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ENOX2
Protein: p.Pro490=
Coding: c.1470T>C
MANE Select: NM_006375
dbSNP: rs143316789
Type: single nucleotide variant
Location: chrX:130631526 (GRCh38)
Structure: AlphaFold pLDDT 77.86

Full ENOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENOX2 c.1129+6G>A Benign ★★ same type
ENOX2 c.-38-6023T>G Uncertain significance ★ ⚠ same type
ENOX2 p.Arg129His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg139His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg156His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg190His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg190Leu Uncertain significance ★ ⚠ same type
ENOX2 p.Arg208His 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/enox2-p-pro490 (accessed [today's date]).

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