Is EHMT1 p.Arg90= (c.268C>A) pathogenic?

EHMT1 p.Arg90= (c.268C>A) is classified Likely benign in EHMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-30). Very rare (popmax 0.00017%, nfe); Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Arg90= (c.268C>A)?

EHMT1 p.Arg90= (c.268C>A) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Arg90= (c.268C>A) in the general population?

EHMT1 p.Arg90= (c.268C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

EHMT1 p.Arg90=

c.268C>A · rs568424578 · VCV1968484

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Kleefstra syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP 0.95, phastCons 0.97
Overall
CADD	7.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,878 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,252 alleles · very rare exomes 2/1,461,068 · genomes 0/152,184 · 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.Arg90=
Coding: c.268C>A
MANE Select: NM_024757
dbSNP: rs568424578
Type: single nucleotide variant
Location: chr9:137716808 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 90: 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.Arg90Gly Uncertain significance ★★ ⚠ same residue
EHMT1 p.Arg90Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
EHMT1 p.Arg90Gln Likely benign ★ same residue
EHMT1 p.Arg90Pro Likely benign ★ 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

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-arg90 (accessed [today's date]).

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