KEAP1 p.Ser508=
c.1524C>T · rs530931137 · VCV716698
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0267%, eas)
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 -3 | GERP -4.6 |
| Overall | ||
| CADD | 3.642 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0267%
East Asian · 12/44,862 alleles
Filtering AF
0.0154%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00211%
34/1,613,666 alleles · ultra-rare
exomes 29/1,461,560 · genomes 5/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0267% | 3,738 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,942 |
| Admixed American | 0.005% | 19,989 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,602 |
| African / African-American | 0.00133% | 74,990 |
| South Asian | 0.0011% | 91,072 |
| European (non-Finnish) | 0.000593% | 168,559 |
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
- KEAP1
- Protein
- p.Ser508=
- Coding
- c.1524C>T
- MANE Select
- NM_203500
- dbSNP
- rs530931137
- Type
- single nucleotide variant
- Location
- chr19:10489655 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI 0.09 (gnomAD)
- Structure
- AlphaFold pLDDT 90.44 · 122 PDB
Similar variants
- KEAP1 p.Ala30= Benign/Likely benign ★★ same type
- KEAP1 p.Val31= Benign/Likely benign ★★ same type
- KEAP1 p.Ala30Val Uncertain significance ★ ⚠ same type
- KEAP1 p.Ala331Val Uncertain significance ★ ⚠ same type
- KEAP1 p.Ala376Thr Uncertain significance ★ ⚠ same type
- KEAP1 p.Ala407Thr Uncertain significance ★ ⚠ same type
- KEAP1 p.Arg15Gln Uncertain significance ★ ⚠ same type
- KEAP1 p.Arg326His 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/keap1-p-ser508 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown