Is EHMT1 p.Pro570= (c.1710G>A) pathogenic?

EHMT1 p.Pro570= (c.1710G>A) is classified Likely benign in EHMT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-02). Very rare (popmax 0.00333%, amr); Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Pro570= (c.1710G>A)?

EHMT1 p.Pro570= (c.1710G>A) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Pro570= (c.1710G>A) in the general population?

EHMT1 p.Pro570= (c.1710G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

EHMT1 p.Pro570=

c.1710G>A · rs746769518 · VCV1140553

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -2.5	GERP -3.9
Overall
CADD	2.603	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,012 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 21/1,613,842 alleles · very rare exomes 17/1,461,656 · genomes 4/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,006
East Asian	0.00223%	44,884
European (non-Finnish)	0.00153%	65,557

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.Pro570=
Coding: c.1710G>A
MANE Select: NM_024757
dbSNP: rs746769518
Type: single nucleotide variant
Location: chr9:137775171 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB

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.Pro570Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
EHMT1 p.Pro570fs Likely pathogenic ★ 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
EHMT1 c.2867+2T>C 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-pro570 (accessed [today's date]).

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