Is EHMT1 p.Phe744fs (c.2214_2230dup) pathogenic?

EHMT1 p.Phe744fs (c.22142230dup) is classified Pathogenic in EHMT1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-03-14). Absent from gnomAD; Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Phe744fs (c.2214_2230dup)?

EHMT1 p.Phe744fs (c.2214_2230dup) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Phe744fs (c.2214_2230dup) in the general population?

EHMT1 p.Phe744fs (c.2214_2230dup) is absent from gnomAD (gnomAD).

EHMT1 p.Phe744fs

c.2214_2230dup · rs1554880275 · VCV438289

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Kleefstra syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EHMT1
Protein: p.Phe744fs
Coding: c.2214_2230dup
MANE Select: NM_024757
dbSNP: rs1554880275
Type: Duplication
Location: chr9:137779655 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 744: an α-helix

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.Phe253fs Pathogenic/Likely pathogenic ★★ same condition
EHMT1 p.Glu531_Ala536dup Uncertain significance ★★ same condition
EHMT1 p.Ala193fs Pathogenic ★ same condition
EHMT1 p.Arg291fs Likely pathogenic ★ same condition
EHMT1 p.Asn1106fs Pathogenic ★ same condition
EHMT1 p.Asn240fs Pathogenic ★ same condition
EHMT1 p.Asn599Ter Pathogenic ★ same condition
EHMT1 p.Asp349fs 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-phe744fs (accessed [today's date]).

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