Is EHMT1 p.Phe253fs (c.756dup) pathogenic?

EHMT1 p.Phe253fs (c.756dup) is classified Pathogenic/Likely pathogenic in EHMT1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-29). No gnomAD frequency available for this variant; Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Phe253fs (c.756dup)?

EHMT1 p.Phe253fs (c.756dup) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Phe253fs (c.756dup) in the general population?

EHMT1 p.Phe253fs (c.756dup) is no gnomAD frequency available for this variant (gnomAD).

EHMT1 p.Phe253fs

c.756dup · rs1554852664 · VCV504217

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

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 4 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -2.5, 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.Phe253fs
Coding: c.756dup
MANE Select: NM_024757
dbSNP: rs1554852664
Type: Duplication
Location: chr9:137728456 (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.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
EHMT1 p.Asp683fs 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-phe253fs (accessed [today's date]).

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