Is EHMT1 p.Arg287Trp (c.859C>T) pathogenic?

EHMT1 p.Arg287Trp (c.859C>T) is classified Uncertain significance in EHMT1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-05). AlphaMissense: likely pathogenic (0.9076); Absent from gnomAD v4.1; Associated with Kleefstra syndrome 1.

What condition is associated with EHMT1 p.Arg287Trp (c.859C>T)?

EHMT1 p.Arg287Trp (c.859C>T) is associated with Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Arg287Trp (c.859C>T) in the general population?

EHMT1 p.Arg287Trp (c.859C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EHMT1 p.Arg287Trp (c.859C>T)?

AlphaMissense predicts likely pathogenic (score 0.9076) — an in-silico prediction, not a clinical call.

EHMT1 p.Arg287Trp

c.859C>T · rs2541599947 · VCV1962327

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9076 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,760)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Kleefstra syndrome 1

Computational evidence

Protein change
AlphaMissense	0.9076	likely pathogenic
REVEL	0.417	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.7, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 144 kb · p 1.3e-07 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,760). 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.Arg287Trp
Coding: c.859C>T
MANE Select: NM_024757
dbSNP: rs2541599947
Type: single nucleotide variant
Location: chr9:137743406 (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.Arg287Gln Conflicting classifications of pathogenicity ★ ⚠ 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
EHMT1 c.3036-1G>A 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-arg287trp (accessed [today's date]).

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