DOT1L p.Arg73=
c.219G>A · rs150316325 · VCV728331
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.78%, eas)
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 4.8 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 11.96 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.78%
East Asian · 1,249/44,882 alleles
Filtering AF
2.65%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.6%
Overall
0.252%
4,064/1,611,814 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 2.78% | 36 |
| Finnishnot grpmax-eligible | 0.404% | 248 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| Ashkenazi Jewishnot grpmax-eligible | 0.287% | 348 |
| European (non-Finnish) | 0.198% | 506 |
| Remaining individualsnot grpmax-eligible | 0.174% | 573 |
| Middle Eastern | 0.0495% | 2,019 |
| South Asian | 0.0198% | 5,060 |
| African / African-American | 0.0147% | 6,823 |
| Admixed American | 0.005% | 20,009 |
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.Arg73=
- Coding
- c.219G>A
- MANE Select
- NM_032482
- dbSNP
- rs150316325
- Type
- single nucleotide variant
- Location
- chr19:2189750 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.11 · 48 PDB
- Residue 73
- the dot1 domain; an α-helix
Similar variants
- DOT1L p.Asp189Asn Uncertain significance ★★ ⚠ same type
- DOT1L p.Ala1101= Benign ★★ same type
- DOT1L p.Arg893= Benign/Likely 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
- DOT1L c.126-2A>G 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/dot1l-p-arg73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown