Is EHMT1 p.Ser680= (c.2040G>A) pathogenic?

EHMT1 p.Ser680= (c.2040G>A) is classified Benign/Likely benign in EHMT1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-19). Rare (popmax 0.513%, afr); Associated with Inborn genetic diseases.

What condition is associated with EHMT1 p.Ser680= (c.2040G>A)?

EHMT1 p.Ser680= (c.2040G>A) is associated with Inborn genetic diseases, Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Ser680= (c.2040G>A) in the general population?

EHMT1 p.Ser680= (c.2040G>A) is rare (popmax 0.513%, afr) (gnomAD).

EHMT1 p.Ser680=

c.2040G>A · rs150451099 · VCV167035

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.513%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.1	GERP -2.6
Overall
CADD	0.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.513% African / African-American · 385/75,010 alleles

Filtering AF 0.471% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.454%

Overall 0.0271% 437/1,613,446 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.513%	195
Middle Eastern	0.0333%	3,007
Remaining individualsnot grpmax-eligible	0.0224%	4,464
Admixed American	0.00666%	15,006
East Asian	0.00446%	22,441
European (non-Finnish)	0.00237%	42,143
South Asian	0.0022%	45,529

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.Ser680=
Coding: c.2040G>A
MANE Select: NM_024757
dbSNP: rs150451099
Type: single nucleotide variant
Location: chr9:137777903 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 680: 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

Also linked: Kleefstra syndrome 1

Similar variants

EHMT1 p.Ser680Leu 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-ser680 (accessed [today's date]).

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