Is EHMT1 p.Pro130= (c.390G>T) pathogenic?

EHMT1 p.Pro130= (c.390G>T) is classified Benign/Likely benign in EHMT1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-01). Ultra-rare (popmax 0.0667%, amr); Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Pro130= (c.390G>T)?

EHMT1 p.Pro130= (c.390G>T) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Pro130= (c.390G>T) in the general population?

EHMT1 p.Pro130= (c.390G>T) is ultra-rare (popmax 0.0667%, amr) (gnomAD).

EHMT1 p.Pro130=

c.390G>T · rs144323841 · VCV462998

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0667%, 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 -2.2	GERP -3.8
Overall
CADD	0.449	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0667% Admixed American · 40/59,994 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.0363% 585/1,612,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0667%	1,500
European (non-Finnish)	0.0445%	2,247
Remaining individualsnot grpmax-eligible	0.0192%	5,207
Middle Eastern	0.0165%	6,058
African / African-American	0.00666%	15,004
Finnishnot grpmax-eligible	0.00317%	31,536

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.Pro130=
Coding: c.390G>T
MANE Select: NM_024757
dbSNP: rs144323841
Type: single nucleotide variant
Location: chr9:137716930 (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.Pro130Leu Likely benign ★★ same residue
EHMT1 p.Pro130Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
EHMT1 p.Pro130_Leu132del Likely benign ★ same residue
EHMT1 p.Pro130Ala 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

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-pro130 (accessed [today's date]).

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