NFE2 p.Ser144=
c.432C>T · rs199698026 · VCV2643056
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.274%, eas)
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 -6.9 | GERP -4.2 |
| Overall | ||
| CADD | 0.796 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.274%
East Asian · 121/44,122 alleles
Filtering AF
0.235%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.22%
Overall
0.013%
198/1,523,634 alleles · rare
exomes 171/1,371,322 · genomes 27/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.274% | 365 |
| South Asian | 0.0631% | 1,584 |
| Middle Eastern | 0.0356% | 2,810 |
| Remaining individualsnot grpmax-eligible | 0.024% | 4,175 |
| Admixed American | 0.00221% | 45,228 |
| European (non-Finnish) | 0.00106% | 94,766 |
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
- NFE2
- Protein
- p.Ser144=
- Coding
- c.432C>T
- MANE Select
- NM_001136023
- dbSNP
- rs199698026
- Type
- single nucleotide variant
- Location
- chr12:54293064 (GRCh38)
- Gene constraint
- LOEUF 0.798 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 67.50 · 1 PDB
- Residue 144
- the 'transactivation domain' region; the 'disordered' region
Similar variants
- NFE2 p.Ala165Gly Uncertain significance ★ ⚠ same type
- NFE2 p.Ala218Val Uncertain significance ★ ⚠ same type
- NFE2 p.Arg168Gln Uncertain significance ★ ⚠ same type
- NFE2 p.Arg169His Uncertain significance ★ ⚠ same type
- NFE2 p.Arg296Gln Uncertain significance ★ ⚠ same type
- NFE2 p.Asn282Thr Uncertain significance ★ ⚠ same type
- NFE2 p.Asp248His Uncertain significance ★ ⚠ same type
- NFE2 p.Asp332Val 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/nfe2-p-ser144 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown