Is EHMT1 p.Val482Ile (c.1444G>A) pathogenic?

EHMT1 p.Val482Ile (c.1444G>A) is classified Conflicting classifications of pathogenicity in EHMT1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-28). AlphaMissense: likely benign (0.1148); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with EHMT1 p.Val482Ile (c.1444G>A)?

EHMT1 p.Val482Ile (c.1444G>A) is associated with Inborn genetic diseases, Kleefstra syndrome 1 (ClinVar).

How common is EHMT1 p.Val482Ile (c.1444G>A) in the general population?

EHMT1 p.Val482Ile (c.1444G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about EHMT1 p.Val482Ile (c.1444G>A)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

EHMT1 p.Val482Ile

c.1444G>A · rs1265023925 · VCV589288

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -7.00	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 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 144 kb · p 1.3e-07 · regional, not allelic
Overall
CADD	25.8	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,614,000 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
European (non-Finnish)	0.000847%	118,004

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.Val482Ile
Coding: c.1444G>A
MANE Select: NM_024757
dbSNP: rs1265023925
Type: single nucleotide variant
Location: chr9:137757954 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Kleefstra syndrome 1

Similar variants

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
EHMT1 c.3259-1G>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-val482ile (accessed [today's date]).

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