Is EHMT1 p.Pro148= (c.444T>C) pathogenic?

EHMT1 p.Pro148= (c.444T>C) is classified Benign in EHMT1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 44.6%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with EHMT1 p.Pro148= (c.444T>C)?

EHMT1 p.Pro148= (c.444T>C) is associated with Inborn genetic diseases, Kleefstra syndrome 1 (ClinVar).

EHMT1 p.Pro148=

Q: How common is EHMT1 p.Pro148= (c.444T>C) in the general population?

EHMT1 p.Pro148= (c.444T>C) is common (popmax 44.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.444T>C · rs3812497 · VCV65738

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 44.6%, amr) — too common for a highly-penetrant pathogenic allele

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 -2.6	GERP -2.1
Overall
CADD	6.184	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 44.6% Admixed American · 26,697/59,836 alleles

Filtering AF 44.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 44%

Overall 27.2% 437,510/1,608,838 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	44.6%	2
Ashkenazi Jewishnot grpmax-eligible	34.8%	3
Amishnot grpmax-eligible	33.4%	3
South Asian	31.7%	3
Middle Eastern	30.1%	3
European (non-Finnish)	27.4%	4
Remaining individualsnot grpmax-eligible	26.4%	4
Finnishnot grpmax-eligible	25.3%	4
East Asian	14.6%	7
African / African-American	11.3%	9

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.Pro148=
Coding: c.444T>C
MANE Select: NM_024757
dbSNP: rs3812497
Type: single nucleotide variant
Location: chr9:137716984 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 148: 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.Pro148Arg Uncertain significance ★ ⚠ 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-pro148 (accessed [today's date]).

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