Is EHMT1 p.Ser1069Tyr (c.3206C>A) pathogenic?

EHMT1 p.Ser1069Tyr (c.3206C>A) is classified Uncertain significance in EHMT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-02). AlphaMissense: likely pathogenic (0.5979); Very rare (popmax 0.000169%, nfe).

How common is EHMT1 p.Ser1069Tyr (c.3206C>A) in the general population?

EHMT1 p.Ser1069Tyr (c.3206C>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about EHMT1 p.Ser1069Tyr (c.3206C>A)?

AlphaMissense predicts likely pathogenic (score 0.5979) — an in-silico prediction, not a clinical call.

EHMT1 p.Ser1069Tyr

c.3206C>A · VCV3602471

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5979 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5979	likely pathogenic
REVEL	0.82	moderately pathogenic-leaning
SaProt	LLR -10.54	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 21 kb · p 1.3e-09 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000169% European (non-Finnish) · 2/1,180,030 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,610,630 alleles · very rare exomes 2/1,458,270 · genomes 0/152,360 · joint denominator

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.Ser1069Tyr
Coding: c.3206C>A
MANE Select: NM_024757
Type: single nucleotide variant
Location: chr9:137814456 (GRCh38)
Gene constraint: LOEUF 0.159 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 22 PDB
Residue 1069: the pre-set domain

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

Similar variants

EHMT1 p.Ser1069Phe 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-ser1069tyr (accessed [today's date]).

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