Is EMX2 p.Ser14= (c.42G>A) pathogenic?

EMX2 p.Ser14= (c.42G>A) is classified Likely benign in EMX2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-19). Ultra-rare (popmax 0.0411%, afr); Associated with EMX2-related disorder.

What condition is associated with EMX2 p.Ser14= (c.42G>A)?

EMX2 p.Ser14= (c.42G>A) is associated with EMX2-related disorder (ClinVar).

How common is EMX2 p.Ser14= (c.42G>A) in the general population?

EMX2 p.Ser14= (c.42G>A) is ultra-rare (popmax 0.0411%, afr) (gnomAD).

EMX2 p.Ser14=

c.42G>A · rs375691102 · VCV3033057

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0411%, afr)

Conditions

EMX2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.46, phastCons 1
Overall
CADD	14.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0411% African / African-American · 30/73,042 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0256%

Overall 0.00219% 34/1,550,878 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0411%	2,435
Remaining individualsnot grpmax-eligible	0.00499%	20,035
Admixed American	0.00196%	51,104

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.Ser14=
Coding: c.42G>A
MANE Select: NM_004098
dbSNP: rs375691102
Type: single nucleotide variant
Location: chr10:117543309 (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

EMX2-related disorder

Similar variants

EMX2 p.Val83Leu Pathogenic ★ same condition
EMX2 p.Ser192Thr Uncertain significance ★★ ⚠ same type
EMX2 c.591+6T>C Benign/Likely benign ★★ same type
EMX2 p.Ala35= Benign/Likely benign ★★ same type
EMX2 p.Arg156= Benign ★★ same type
EMX2 p.Lys199Gln Likely pathogenic ★ same type
EMX2 p.Ala172Asp Uncertain significance ★ ⚠ same type
EMX2 p.Ala172Thr Uncertain significance ★ ⚠ 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/emx2-p-ser14 (accessed [today's date]).

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