EHMT1 p.Asp351=
c.1053C>T · rs779549255 · VCV2041537
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Conditions
1
Kleefstra syndrome 1
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 -14 | GERP -3.3 |
| Overall | ||
| CADD | 2.033 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,056 alleles
Filtering AF
0.000739%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000753%
11/1,461,610 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,056 |
| East Asian | 0.00446% | 22,439 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,248 |
| African / African-American | 0.00133% | 75,050 |
| European (non-Finnish) | 0.000424% | 235,991 |
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
- EHMT1
- Protein
- p.Asp351=
- Coding
- c.1053C>T
- MANE Select
- NM_024757
- dbSNP
- rs779549255
- Type
- single nucleotide variant
- Location
- chr9:137743973 (GRCh38)
- Gene constraint
- LOEUF 0.159 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 64.89 · 22 PDB
- Residue 351
- the 'disordered' region
Similar variants
- EHMT1 p.Asp351Val Uncertain significance ★ ⚠ same residue
- EHMT1 p.Asp351Glu Benign ★ same residue
- EHMT1 p.Asp351fs Pathogenic ★★ same residue
- EHMT1 p.Asp351Gly Uncertain significance ★ ⚠ same residue
- EHMT1 p.Asp351Tyr Uncertain significance ★ ⚠ same residue
- EHMT1 c.1370-1G>C Likely pathogenic ★★ same condition
- EHMT1 c.1647+2T>C Pathogenic/Likely pathogenic ★★ same condition
- EHMT1 c.2193-1G>C Pathogenic ★★ same condition
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/ehmt1-p-asp351 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown