DOT1L p.Ser1450=
c.4350C>T · VCV4280779
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.24%, sas)
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 -5.4 | GERP -2.3 |
| Overall | ||
| CADD | 0.148 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.24%
South Asian · 1,092/88,052 alleles
Filtering AF
1.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.15%
Overall
0.322%
5,068/1,572,576 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.24% | 81 |
| Remaining individualsnot grpmax-eligible | 0.384% | 261 |
| European (non-Finnish) | 0.306% | 326 |
| Middle Eastern | 0.275% | 364 |
| Admixed American | 0.121% | 825 |
| Finnishnot grpmax-eligible | 0.0954% | 1,048 |
| African / African-American | 0.0361% | 2,767 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0105% | 9,496 |
| East Asian | 0.00706% | 14,171 |
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.Ser1450=
- Coding
- c.4350C>T
- MANE Select
- NM_032482
- Type
- single nucleotide variant
- Location
- chr19:2226871 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.11 · 48 PDB
Similar variants
- DOT1L p.Asp189Asn Uncertain significance ★★ ⚠ same type
- DOT1L p.Ala1101= Benign ★★ same type
- DOT1L p.Arg73= 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
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-ser1450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown