Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 26.5%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
Inborn genetic diseases
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 -8.3 | GERP -4.9 |
| Overall | ||
| CADD | 0.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
26.5%
East Asian · 11,890/44,872 alleles
Filtering AF
26.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 25.9%
Overall
9.34%
150,723/1,613,850 alleles · common
exomes 134,800/1,461,634 · genomes 15,923/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 26.5% | 4 |
| South Asian | 20.6% | 5 |
| Admixed American | 16.2% | 6 |
| Finnishnot grpmax-eligible | 11.8% | 8 |
| Remaining individualsnot grpmax-eligible | 11% | 9 |
| Middle Eastern | 11% | 9 |
| Ashkenazi Jewishnot grpmax-eligible | 11% | 9 |
| African / African-American | 10.7% | 9 |
| European (non-Finnish) | 7.11% | 14 |
| Amishnot grpmax-eligible | 3.95% | 25 |
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
- KAT6A
- Protein
- p.Pro994=
- Coding
- c.2982G>A
- MANE Select
- NM_006766
- dbSNP
- rs3824275
- Type
- single nucleotide variant
- Location
- chr8:41940899 (GRCh38)
- Gene constraint
- LOEUF 0.083 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 49.12 · 21 PDB
- Residue 994
- the 'disordered' region
Similar variants
- KAT6A p.Pro994Leu Benign/Likely benign ★★ same residue
- KAT6A p.Pro994Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- KAT6A p.Pro994Gln Benign ★ same residue
- KAT6A p.Arg1129Ter Pathogenic ★★ same condition
- KAT6A p.Arg148Ter Pathogenic ★★ same condition
- KAT6A p.Arg286Ter Pathogenic ★★ same condition
- KAT6A p.Arg735Ter Pathogenic ★★ same condition
- KAT6A p.Ala1451Gly Uncertain significance ★★ ⚠ same condition
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/kat6a-p-pro994 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown