Is EHMT1 p.Arg951His (c.2852G>A) pathogenic?

EHMT1 p.Arg951His (c.2852G>A) is classified Uncertain significance in EHMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-19). AlphaMissense: likely benign (0.2264); Very rare (popmax 0.00133%, afr).

How common is EHMT1 p.Arg951His (c.2852G>A) in the general population?

EHMT1 p.Arg951His (c.2852G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about EHMT1 p.Arg951His (c.2852G>A)?

AlphaMissense predicts likely benign (score 0.2264) — an in-silico prediction, not a clinical call.

EHMT1 p.Arg951His

c.2852G>A · rs1202437743 · VCV2430864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2264	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -6.72	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 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 35 kb · p 1.6e-15 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,944 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000312% 5/1,602,342 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,944
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,323

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.Arg951His
Coding: c.2852G>A
MANE Select: NM_024757
dbSNP: rs1202437743
Type: single nucleotide variant
Location: chr9:137811600 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB

Full EHMT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EHMT1 p.Arg951Cys Likely benign ★ same residue
EHMT1 c.1370-1G>C Likely pathogenic ★★ same type
EHMT1 c.1647+2T>C Pathogenic/Likely pathogenic ★★ same type
EHMT1 c.2193-1G>C Pathogenic ★★ same type
EHMT1 c.2276-2A>G Pathogenic ★★ same type
EHMT1 c.2712+1G>A Pathogenic ★★ same type
EHMT1 c.2867+2T>C Pathogenic/Likely pathogenic ★★ same type
EHMT1 c.3036-1G>A Pathogenic/Likely pathogenic ★★ 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/ehmt1-p-arg951his (accessed [today's date]).

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