Is EHMT1 p.Ala6= (c.18C>G) pathogenic?

EHMT1 p.Ala6= (c.18C>G) is classified Likely benign in EHMT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-01). Very rare (popmax 0.000497%, nfe); Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Ala6= (c.18C>G)?

EHMT1 p.Ala6= (c.18C>G) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Ala6= (c.18C>G) in the general population?

EHMT1 p.Ala6= (c.18C>G) is very rare (popmax 0.000497%, nfe) (gnomAD).

EHMT1 p.Ala6=

c.18C>G · rs1588999893 · VCV2817751

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000497%, nfe)

Conditions

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 -0.65	GERP -0.54, phastCons 0.22
Overall
CADD	12.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000497% European (non-Finnish) · 4/804,486 alleles

Filtering AF 0.000116% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.9e-05%

Overall 0.000419% 4/954,976 alleles · very rare exomes 4/809,040 · genomes 0/145,936 · joint denominator

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.Ala6=
Coding: c.18C>G
MANE Select: NM_024757
dbSNP: rs1588999893
Type: single nucleotide variant
Location: chr9:137619046 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 6: the 'disordered' region

Full EHMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Kleefstra syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EHMT1 p.Ala6Thr Uncertain significance ★ ⚠ same residue
EHMT1 p.Ala6Val Likely benign ★ same residue
EHMT1 p.Ala6Pro 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
EHMT1 c.2276-2A>G Pathogenic ★★ same condition
EHMT1 c.2712+1G>A 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-ala6 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown