Is EHMT1 p.Arg1245= (c.3735C>T) pathogenic?

EHMT1 p.Arg1245= (c.3735C>T) is classified Benign/Likely benign in EHMT1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-03-01). Rare (popmax 0.281%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EHMT1 p.Arg1245= (c.3735C>T)?

EHMT1 p.Arg1245= (c.3735C>T) is associated with Inborn genetic diseases, Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Arg1245= (c.3735C>T) in the general population?

EHMT1 p.Arg1245= (c.3735C>T) is rare (popmax 0.281%, nfe) (gnomAD).

EHMT1 p.Arg1245=

c.3735C>T · rs141797498 · VCV96160

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

rare (popmax 0.281%, nfe)

Conditions

Inborn genetic diseases

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 1.1	GERP -0.46, phastCons 1
Overall
CADD	11.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% European (non-Finnish) · 3,319/1,179,738 alleles

Filtering AF 0.273% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.23% 3,718/1,613,250 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.281%	355
Remaining individualsnot grpmax-eligible	0.245%	408
Admixed American	0.213%	469
African / African-American	0.105%	950
Ashkenazi Jewishnot grpmax-eligible	0.0744%	1,345
Middle Eastern	0.0167%	5,984
Finnishnot grpmax-eligible	0.011%	9,087
South Asian	0.00988%	10,120

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.Arg1245=
Coding: c.3735C>T
MANE Select: NM_024757
dbSNP: rs141797498
Type: single nucleotide variant
Location: chr9:137834791 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 1245: an α-helix; the 'interaction with histone h3' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Kleefstra syndrome 1

Similar variants

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
EHMT1 c.2867+2T>C Pathogenic/Likely pathogenic ★★ same condition
EHMT1 c.3036-1G>A Pathogenic/Likely pathogenic ★★ same condition
EHMT1 c.3259-1G>A Pathogenic/Likely 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-arg1245 (accessed [today's date]).

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