DOT1L p.Pro1231=
c.3693C>T · VCV3771065
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, nfe)
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 -8.5 | GERP -2.8 |
| Overall | ||
| CADD | 0.194 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
European (non-Finnish) · 243/1,135,064 alleles
Filtering AF
0.0191%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0183%
Overall
0.0172%
263/1,527,150 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0214% | 4,671 |
| East Asian | 0.00926% | 10,800 |
| Remaining individualsnot grpmax-eligible | 0.00852% | 11,741 |
| South Asian | 0.00642% | 15,569 |
| African / African-American | 0.00553% | 18,089 |
| Admixed American | 0.00404% | 24,749 |
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.Pro1231=
- Coding
- c.3693C>T
- MANE Select
- NM_032482
- Type
- single nucleotide variant
- Location
- chr19:2226214 (GRCh38)
- Gene constraint
- LOEUF 0.321 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 54.11 · 48 PDB
- Residue 1231
- the 'disordered' region
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-pro1231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown