Is EHMT1 p.Pro678fs (c.2031dup) pathogenic?

EHMT1 p.Pro678fs (c.2031dup) is classified Pathogenic in EHMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-28). Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Pro678fs (c.2031dup)?

EHMT1 p.Pro678fs (c.2031dup) is associated with Kleefstra syndrome 1 (ClinVar).

EHMT1 p.Pro678fs

c.2031dup · VCV3901168

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 13 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.6	GERP 0.36, phastCons 0.008

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

Variant & gene context

Gene: EHMT1
Protein: p.Pro678fs
Coding: c.2031dup
MANE Select: NM_024757
Type: Duplication
Location: chr9:137777893 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 678: 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.Pro678= Likely benign ★ same residue
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

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-pro678fs (accessed [today's date]).

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