NFE2L2 p.Ser342=
c.1026T>C · rs747873842 · VCV1531060
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00636%, 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 0.74 | GERP -2, phastCons 0.95 |
| Overall | ||
| CADD | 6.651 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00636%
European (non-Finnish) · 75/1,180,038 alleles
Filtering AF
0.00519%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00474%
Overall
0.00471%
76/1,614,118 alleles · very rare
exomes 72/1,461,880 · genomes 4/152,238 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00636% | 15,734 |
| Admixed American | 0.00167% | 60,012 |
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.Ser342=
- Coding
- c.1026T>C
- MANE Select
- NM_006164
- dbSNP
- rs747873842
- Type
- single nucleotide variant
- Location
- chr2:177231577 (GRCh38)
- Gene constraint
- LOEUF 0.575 · pLI 0.50 (gnomAD)
- Structure
- AlphaFold pLDDT 61.72 · 23 PDB
- Residue 342
- the 'disordered' region
Similar variants
- 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
- NFE2L2 p.Asn225Ser Uncertain significance ★★ ⚠ same type
- NFE2L2 p.Asn278Ser 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-ser342 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown