Is EHMT1 p.Arg552Trp (c.1654C>T) pathogenic?

EHMT1 p.Arg552Trp (c.1654C>T) is classified Uncertain significance in EHMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: ambiguous (0.4026); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with EHMT1 p.Arg552Trp (c.1654C>T)?

EHMT1 p.Arg552Trp (c.1654C>T) is associated with Inborn genetic diseases (ClinVar).

How common is EHMT1 p.Arg552Trp (c.1654C>T) in the general population?

EHMT1 p.Arg552Trp (c.1654C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about EHMT1 p.Arg552Trp (c.1654C>T)?

AlphaMissense predicts ambiguous (score 0.4026) — an in-silico prediction, not a clinical call.

EHMT1 p.Arg552Trp

c.1654C>T · VCV4017016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4026	ambiguous
REVEL	0.364	indeterminate
SaProt	LLR -13.63	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP -1.9, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 14 kb · p 1.5e-07 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.00167% Admixed American · 1/60,024 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00123% 18/1,461,782 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
European (non-Finnish)	0.00136%	73,751
South Asian	0.0011%	91,086

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.Arg552Trp
Coding: c.1654C>T
MANE Select: NM_024757
Type: single nucleotide variant
Location: chr9:137775115 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EHMT1 p.Arg552Gln Likely benign ★★ ⚠ same residue
EHMT1 p.Arg552= Likely benign ★ same residue
EHMT1 c.2193-1G>C Pathogenic ★★ same condition
EHMT1 p.Arg1116Ter Pathogenic ★★ same condition
EHMT1 p.Arg291Ter Pathogenic ★★ same condition
EHMT1 p.Arg490Ter Pathogenic/Likely pathogenic ★★ same condition
EHMT1 p.Trp437Ter Pathogenic/Likely pathogenic ★★ same condition
EHMT1 c.3461+3G>A Uncertain significance ★★ 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-arg552trp (accessed [today's date]).

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