DOT1L p.Arg893=
c.2679C>T · rs544749605 · VCV721697
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.216%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.262 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3 |
| Overall | ||
| CADD | 0.542 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.216%
Middle Eastern · 13/6,008 alleles
Filtering AF
0.163%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.154%
Overall
0.0217%
349/1,611,968 alleles · rare
exomes 331/1,459,630 · genomes 18/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.216% | 462 |
| South Asian | 0.186% | 538 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,468 |
| East Asian | 0.0134% | 7,479 |
| Admixed American | 0.0133% | 7,492 |
| European (non-Finnish) | 0.011% | 9,075 |
| African / African-American | 0.00533% | 18,762 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,548 |
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
- DOT1L
- Protein
- p.Arg893=
- Coding
- c.2679C>T
- MANE Select
- NM_032482
- dbSNP
- rs544749605
- Type
- single nucleotide variant
- Location
- chr19:2217906 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.11 · 48 PDB
- Residue 893
- the 'disordered' region
Similar variants
- DOT1L p.Arg893Cys Uncertain significance ★ ⚠ same residue
- DOT1L p.Asp189Asn Uncertain significance ★★ ⚠ same type
- DOT1L p.Ala1101= Benign ★★ same type
- DOT1L p.Arg73= Benign ★★ same type
- DOT1L p.Asp155= Benign ★★ same type
- DOT1L p.Pro758= Likely benign ★★ same type
- DOT1L p.Thr1068= Benign/Likely benign ★★ same type
- DOT1L p.Thr957Ile Likely benign ★★ 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/dot1l-p-arg893 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown