Is EMX2 p.Thr207= (c.621A>C) pathogenic?

EMX2 p.Thr207= (c.621A>C) is classified Likely benign in EMX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EMX2 p.Thr207= (c.621A>C)?

EMX2 p.Thr207= (c.621A>C) is associated with Inborn genetic diseases (ClinVar).

How common is EMX2 p.Thr207= (c.621A>C) in the general population?

EMX2 p.Thr207= (c.621A>C) is very rare (popmax 0.000509%, nfe) (gnomAD).

EMX2 p.Thr207=

c.621A>C · rs993844229 · VCV2557719

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.016	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -5.6, phastCons 0.009
Overall
CADD	8.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,596 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000411% 6/1,460,970 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.Thr207=
Coding: c.621A>C
MANE Select: NM_004098
dbSNP: rs993844229
Type: single nucleotide variant
Location: chr10:117548094 (GRCh38)
Gene constraint: LOEUF 0.499 · pLI 0.98 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 67.26
Residue 207: a DNA-binding region

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-thr207 (accessed [today's date]).

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