NFE2L2 p.Pro128=
c.384G>A · rs199970826 · VCV1901069
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00951%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | GERP -3.7 |
| Overall | ||
| CADD | 7.016 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00951%
African / African-American · 7/73,622 alleles
Filtering AF
0.00444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00313%
Overall
0.00332%
53/1,595,378 alleles · very rare
exomes 49/1,443,212 · genomes 4/152,166 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00951% | 10,517 |
| East Asian | 0.00682% | 14,667 |
| Remaining individualsnot grpmax-eligible | 0.00486% | 20,587 |
| South Asian | 0.00345% | 29,017 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00344% | 29,048 |
| European (non-Finnish) | 0.00306% | 32,638 |
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
- NFE2L2
- Protein
- p.Pro128=
- Coding
- c.384G>A
- MANE Select
- NM_006164
- dbSNP
- rs199970826
- Type
- single nucleotide variant
- Location
- chr2:177233268 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.50 (gnomAD)
- Structure
- AlphaFold pLDDT 61.72 · 23 PDB
Similar variants
- NFE2L2 p.Pro128Gln Uncertain significance ★ ⚠ same residue
- NFE2L2 p.Pro128Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- NFE2L2 p.Ala249Ser Uncertain significance ★★ ⚠ same type
- NFE2L2 p.Ala496Gly Uncertain significance ★★ ⚠ same type
- NFE2L2 p.Arg34Gln Uncertain significance ★★ ⚠ same type
- NFE2L2 p.Arg449Cys Uncertain significance ★★ ⚠ same type
- NFE2L2 p.Arg569Cys Uncertain significance ★★ ⚠ same type
- NFE2L2 p.Asn101Ser 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/nfe2l2-p-pro128 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown