KDM1A p.Asp554=
c.1662T>C · rs75011666 · VCV781581
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 5.26%, eas) — too common for a highly-penetrant pathogenic allele
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 -0.56 | GERP 0.28, phastCons 0.056 |
| Overall | ||
| CADD | 7.629 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.26%
East Asian · 2,359/44,852 alleles
Filtering AF
5.08%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.01%
Overall
0.239%
3,848/1,611,494 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 5.26% | 19 |
| Admixed American | 1.21% | 83 |
| Remaining individualsnot grpmax-eligible | 0.232% | 431 |
| Ashkenazi Jewishnot grpmax-eligible | 0.166% | 604 |
| South Asian | 0.155% | 646 |
| Finnishnot grpmax-eligible | 0.138% | 722 |
| Middle Eastern | 0.115% | 866 |
| African / African-American | 0.0906% | 1,103 |
| European (non-Finnish) | 0.0224% | 4,462 |
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
- KDM1A
- Protein
- p.Asp554=
- Coding
- c.1662T>C
- MANE Select
- NM_001009999
- dbSNP
- rs75011666
- Type
- single nucleotide variant
- Location
- chr1:23073331 (GRCh38)
- Gene constraint
- LOEUF 0.638 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.29 · 129 PDB
- Residue 554
- the 'demethylase activity' region; a UniProt-annotated variant site (in aimah3; likely pathogenic; loss of protein expression in patient adrenal samples); a UniProt-annotated variant site (in aimah3; likely pathogenic); a turn
Similar variants
- KDM1A p.Asp399Gly Likely pathogenic ★★ same type
- KDM1A p.Asp580Gly Pathogenic/Likely pathogenic ★★ same type
- KDM1A p.Ala10Val Uncertain significance ★★ ⚠ same type
- KDM1A p.Ala11Ser Uncertain significance ★★ ⚠ same type
- KDM1A p.Ala11Thr Uncertain significance ★★ ⚠ same type
- KDM1A p.Ala12Val Uncertain significance ★★ ⚠ same type
- KDM1A p.Ala13Thr Uncertain significance ★★ ⚠ same type
- KDM1A p.Ala18Thr 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/kdm1a-p-asp554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown