DOT1L p.Ala368=
c.1104C>T · rs142127010 · VCV720086
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -9.8 | GERP -2.4 |
| Overall | ||
| CADD | 0.087 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
African / African-American · 795/74,520 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.981%
Overall
0.0578%
922/1,594,396 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.07% | 94 |
| Remaining individualsnot grpmax-eligible | 0.0877% | 1,141 |
| Admixed American | 0.0707% | 1,415 |
| Middle Eastern | 0.0535% | 1,868 |
| South Asian | 0.00554% | 18,054 |
| Finnishnot grpmax-eligible | 0.00514% | 19,450 |
| East Asian | 0.0045% | 22,237 |
| European (non-Finnish) | 0.00162% | 61,661 |
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.Ala368=
- Coding
- c.1104C>T
- MANE Select
- NM_032482
- dbSNP
- rs142127010
- Type
- single nucleotide variant
- Location
- chr19:2210498 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.11 · 48 PDB
- Residue 368
- the 'disordered' region; the 'required for dna binding and full methyltransferase activity' region
Similar variants
- DOT1L p.Ala368Thr Likely benign ★ same residue
- 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
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-ala368 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown