Is EHMT2 p.Glu450Asp (c.1350G>C) pathogenic?

EHMT2 p.Glu450Asp (c.1350G>C) is classified Uncertain significance in EHMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely pathogenic (0.8702); Very rare (popmax 0.00666%, amr).

How common is EHMT2 p.Glu450Asp (c.1350G>C) in the general population?

EHMT2 p.Glu450Asp (c.1350G>C) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about EHMT2 p.Glu450Asp (c.1350G>C)?

AlphaMissense predicts likely pathogenic (score 0.8702) — an in-silico prediction, not a clinical call.

EHMT2 p.Glu450Asp

c.1350G>C · VCV3507440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8702 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8702	likely pathogenic
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.73	GERP -0.88, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 5,669 bp · p 7.9e-23 · regional, not allelic
Overall
CADD	18.67	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 0.00666% Admixed American · 4/60,024 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00031% 5/1,613,218 alleles · very rare exomes 3/1,460,906 · genomes 2/152,312 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,006
South Asian	0.0011%	91,082

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: EHMT2
Protein: p.Glu450Asp
Coding: c.1350G>C
MANE Select: NM_006709
Type: single nucleotide variant
Location: chr6:31888614 (GRCh38)
Gene constraint: LOEUF 0.492 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 69.25 · 34 PDB
Residue 450: a β-strand

Full EHMT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHMT2 p.Ala1077Thr Pathogenic ★★ same type
EHMT2 p.Ala1077Ser Pathogenic ★ same type
EHMT2 p.Asn1112Ser Pathogenic ★ ⚠ same type
EHMT2 p.Lys1162Arg Pathogenic ★ same type
EHMT2 p.Phe1158Leu Pathogenic ★ same type
EHMT2 c.328+2T>G Uncertain significance ★ same type
EHMT2 p.Ala137Ser Uncertain significance ★ ⚠ same type
EHMT2 p.Ala17Pro Uncertain significance ★ ⚠ same type

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/ehmt2-p-glu450asp (accessed [today's date]).

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