Is EHMT2 p.Ile700Phe (c.2098A>T) pathogenic?

EHMT2 p.Ile700Phe (c.2098A>T) is classified Uncertain significance in EHMT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-02). AlphaMissense: likely pathogenic (0.8316); Very rare (popmax 0.0011%, nfe).

How common is EHMT2 p.Ile700Phe (c.2098A>T) in the general population?

EHMT2 p.Ile700Phe (c.2098A>T) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about EHMT2 p.Ile700Phe (c.2098A>T)?

AlphaMissense predicts likely pathogenic (score 0.8316) — an in-silico prediction, not a clinical call.

EHMT2 p.Ile700Phe

c.2098A>T · VCV4663545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8316 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8316	likely pathogenic
REVEL	0.509	indeterminate
SaProt	LLR -9.21	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 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 5,669 bp · p 7.9e-23 · regional, not allelic
Overall
CADD	26.8	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 0.0011% European (non-Finnish) · 13/1,180,020 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000889% 13/1,461,650 alleles · very rare

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.Ile700Phe
Coding: c.2098A>T
MANE Select: NM_006709
Type: single nucleotide variant
Location: chr6:31887015 (GRCh38)
Gene constraint: LOEUF 0.492 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 69.25 · 34 PDB

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-ile700phe (accessed [today's date]).

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