Is EMX2 p.Thr139Ala (c.415A>G) pathogenic?

EMX2 p.Thr139Ala (c.415A>G) is classified Uncertain significance in EMX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0652); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EMX2 p.Thr139Ala (c.415A>G)?

EMX2 p.Thr139Ala (c.415A>G) is associated with Inborn genetic diseases (ClinVar).

How common is EMX2 p.Thr139Ala (c.415A>G) in the general population?

EMX2 p.Thr139Ala (c.415A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about EMX2 p.Thr139Ala (c.415A>G)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

EMX2 p.Thr139Ala

c.415A>G · VCV4017914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -5.61	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 6.1	GERP 0.96, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 2,389 bp · p 0.33 · regional, not allelic
Overall
CADD	19.25	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 8.47e-05% European (non-Finnish) · 1/1,180,026 alleles

Overall 6.84e-05% 1/1,461,704 alleles · very rare

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: EMX2
Protein: p.Thr139Ala
Coding: c.415A>G
MANE Select: NM_004098
Type: single nucleotide variant
Location: chr10:117545640 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.98 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 67.26

Full EMX2 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

Similar variants

EMX2 p.Ala172Asp Uncertain significance ★ ⚠ same condition
EMX2 p.Ala172Thr Uncertain significance ★ ⚠ same condition
EMX2 p.Ala34Val Uncertain significance ★ ⚠ same condition
EMX2 p.Ala5Gly Uncertain significance ★ ⚠ same condition
EMX2 p.Ala5Pro Uncertain significance ★ ⚠ same condition
EMX2 p.Ala95Val Uncertain significance ★ ⚠ same condition
EMX2 p.Arg114Gly Uncertain significance ★ ⚠ same condition
EMX2 p.Asn80Asp Uncertain significance ★ ⚠ 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/emx2-p-thr139ala (accessed [today's date]).

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