Is EHMT1 p.Pro709Ala (c.2125C>G) pathogenic?

EHMT1 p.Pro709Ala (c.2125C>G) is classified Likely benign in EHMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-25). AlphaMissense: likely benign (0.0504); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EHMT1 p.Pro709Ala (c.2125C>G)?

EHMT1 p.Pro709Ala (c.2125C>G) is associated with Inborn genetic diseases (ClinVar).

How common is EHMT1 p.Pro709Ala (c.2125C>G) in the general population?

EHMT1 p.Pro709Ala (c.2125C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EHMT1 p.Pro709Ala (c.2125C>G)?

AlphaMissense predicts likely benign (score 0.0504) — an in-silico prediction, not a clinical call.

EHMT1 p.Pro709Ala

c.2125C>G · rs1417694539 · VCV1786308

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0504 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0504	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -2.7
Regional constraint	o/e 0.97	unconstrained · MANE · 1,208 bp · p 0.79 · regional, not allelic
Overall
CADD	3.869	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EHMT1
Protein: p.Pro709Ala
Coding: c.2125C>G
MANE Select: NM_024757
dbSNP: rs1417694539
Type: single nucleotide variant
Location: chr9:137777988 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 709: the 'disordered' region

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.Pro709= 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
EHMT1 c.-5G>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-pro709ala (accessed [today's date]).

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